Recent epigenetics publications from Alberta researchers.

2015

  • D. Z. Kochan and O. Kovalchuk, “Circadian disruption and breast cancer: An epigenetic link?,” Oncotarget, vol. 6, iss. 19, pp. 16866-16882, 2015.
    [Bibtex]
    @Article{pmid26220712,
    Author="Kochan, D. Z. and Kovalchuk, O. ",
    Title="{{C}ircadian disruption and breast cancer: {A}n epigenetic link?}",
    Journal="Oncotarget",
    Year="2015",
    Volume="6",
    Number="19",
    Pages="16866--16882",
    Month="Jul"
    }
  • D. Z. Kochan, Y. Ilnytskyy, A. Golubov, S. H. Deibel, R. J. McDonald, and O. Kovalchuk, “Circadian disruption-induced microRNAome deregulation in rat mammary gland tissues,” Oncoscience, vol. 2, iss. 4, pp. 428-442, 2015.
    [Bibtex]
    @Article{pmid26097876,
    Author="Kochan, D. Z. and Ilnytskyy, Y. and Golubov, A. and Deibel, S. H. and McDonald, R. J. and Kovalchuk, O. ",
    Title="{{C}ircadian disruption-induced micro{R}{N}{A}ome deregulation in rat mammary gland tissues}",
    Journal="Oncoscience",
    Year="2015",
    Volume="2",
    Number="4",
    Pages="428--442"
    }
  • I. Christiaens, K. Hegadoren, and D. M. Olson, “Adverse childhood experiences are associated with spontaneous preterm birth: a case-control study,” Bmc med, vol. 13, p. 124, 2015.
    [Bibtex]
    @Article{pmid26063042,
    Author="Christiaens, I. and Hegadoren, K. and Olson, D. M. ",
    Title="{{A}dverse childhood experiences are associated with spontaneous preterm birth: a case-control study}",
    Journal="BMC Med",
    Year="2015",
    Volume="13",
    Pages="124",
    Abstract={More than 1 in 10 infants are born prematurely worldwide, making preterm birth the leading cause of neonatal mortality and morbidity. Chronic maternal stress is increasingly recognized as one of the contributing risk factors for preterm birth, yet its specific role remains largely unknown. Examining the exposure to stressors over a mother's life course might provide more perspective on the role of maternal stress in preterm birth. Our aim was therefore to retrospectively explore the associations between chronic, lifelong stressors and protective factors and spontaneous preterm birth.\\ This study was part of a large case-control study based in Edmonton, Canada, examining gene-environment interactions and preterm birth. Cases were mothers with a spontaneous singleton preterm birth (<37 weeks) without preterm premature rupture of membranes. Controls were mothers with an uncomplicated singleton term birth without a history of preterm birth. Sociodemographic and medical data were collected. A postpartum telephone questionnaire was administered to assess stressors across the lifespan. Both individual and contextual variables that could influence stress response systems were examined. Overall, 622 women were included, of which 223 subjects - 75 cases and 148 controls - completed the stress questionnaire. Univariate and multivariate logistic regression analyses were performed.\\ Multivariate analysis showed that exposure to two or more adverse childhood experiences (ACEs) was associated with a two-fold risk of preterm birth, regardless of maternal age, smoking status, educational status, and history of miscarriage (adjusted OR, 2.09; 95 % CI, 1.10-3.98; P = 0.024). The adjusted odds ratio for the ACE score was 1.18 (95 % CI, 0.99-1.40), suggesting that for every increase in childhood adverse event endorsed, the risk of preterm birth increased by 18 %. Lifetime physical and emotional abuse was also associated with spontaneous preterm birth in our study population (adjusted OR, 1.30; 95 % CI, 1.02-1.65; P = 0.033).\\ A strong relationship between ACEs and preterm birth was observed. It has been shown that two or more ACEs have a notable two-fold increase in the risk of spontaneous preterm birth. These data demonstrate that stressors throughout life can have a significant effect on pregnancy outcomes such as preterm birth.},
    Note={[PubMed Central:\href{http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4464612}{PMC4464612}] [DOI:\href{http://dx.doi.org/10.1186/s12916-015-0353-0}{10.1186/s12916-015-0353-0}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/26063042}{26063042}] }
    }
  • A. Harker, S. Raza, K. Williamson, B. Kolb, and R. Gibb, “Preconception paternal stress in rats alters dendritic morphology and connectivity in the brain of developing male and female offspring,” Neuroscience, 2015.
    [Bibtex]
    @Article{pmid26149350,
    Author="Harker, A. and Raza, S. and Williamson, K. and Kolb, B. and Gibb, R. ",
    Title="{{P}reconception paternal stress in rats alters dendritic morphology and connectivity in the brain of developing male and female offspring}",
    Journal="Neuroscience",
    Year="2015",
    Pages=" ",
    Month="Jul",
    Abstract={The goal of this research was to examine the effect of preconception paternal stress (PPS) on the subsequent neurodevelopment and behavior of male and female offspring. Prenatal (gestational) stress has been shown to alter brain morphology in the developing brain, and is presumed to be a factor in the development of some adult psychopathologies. Our hypothesis was that paternal stress (PS) in the preconception period could impact brain development in the offspring, leading to behavioral abnormalities later in life. The purpose of this study was to examine the effect of preconception paternal stress on developing male and female offspring brain morphology in five brain areas; medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), parietal cortex (Par1), hippocampus (CA1) and nucleus accumbens (NAc). Alterations in dendritic measures and spine density were observed in each brain area examined in PS offspring. Our two main findings reveal; (1) PPS alters brain morphology and organization and these effects are different than the effects of stress observed at other ages; and, (2) the observed dendritic changes were sexually dimorphic. This study provides direct evidence that PPS modifies brain architecture in developing offspring, including dendritic length, cell complexity, and spine density. Alterations observed may contribute to the later development of psychopathologies and maladaptive behaviors in the offspring.},
    Note={[DOI:\href{http://dx.doi.org/10.1016/j.neuroscience.2015.06.058}{10.1016/j.neuroscience.2015.06.058}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/26149350}{26149350}] }
    }
  • I. Abdou, G. G. Poirier, M. J. Hendzel, and M. Weinfeld, “DNA ligase III acts as a DNA strand break sensor in the cellular orchestration of DNA strand break repair,” Nucleic acids res., vol. 43, iss. 2, pp. 875-892, 2015.
    [Bibtex]
    @Article{pmid25539916,
    Author="Abdou, I. and Poirier, G. G. and Hendzel, M. J. and Weinfeld, M. ",
    Title="{{D}{N}{A} ligase {I}{I}{I} acts as a {D}{N}{A} strand break sensor in the cellular orchestration of {D}{N}{A} strand break repair}",
    Journal="Nucleic Acids Res.",
    Year="2015",
    Volume="43",
    Number="2",
    Pages="875--892",
    Month="Jan",
    Abstract={In the current model of DNA SSBR, PARP1 is regarded as the sensor of single-strand breaks (SSBs). However, biochemical studies have implicated LIG3 as another possible SSB sensor. Using a laser micro-irradiation protocol that predominantly generates SSBs, we were able to demonstrate that PARP1 is dispensable for the accumulation of different single-strand break repair (SSBR) proteins at sites of DNA damage in live cells. Furthermore, we show in live cells for the first time that LIG3 plays a role in mediating the accumulation of the SSBR proteins XRCC1 and PNKP at sites of DNA damage. Importantly, the accumulation of LIG3 at sites of DNA damage did not require the BRCT domain-mediated interaction with XRCC1. We were able to show that the N-terminal ZnF domain of LIG3 plays a key role in the enzyme's SSB sensing function. Finally, we provide cellular evidence that LIG3 and not PARP1 acts as the sensor for DNA damage caused by the topoisomerase I inhibitor, irinotecan. Our results support the existence of a second damage-sensing mechanism in SSBR involving the detection of nicks in the genome by LIG3.},
    Note={[PubMed Central:\href{http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4333375}{PMC4333375}] [DOI:\href{http://dx.doi.org/10.1093/nar/gku1307}{10.1093/nar/gku1307}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/25539916}{25539916}] }
    }
  • U. M. Tran, U. Rajarajacholan, J. Soh, T. S. Kim, S. Thalappilly, C. W. Sensen, and K. Riabowol, “LincRNA-p21 acts as a mediator of ING1b-induced apoptosis,” Cell death dis, vol. 6, p. e1668, 2015.
    [Bibtex]
    @Article{pmid25741593,
    Author="Tran, U. M. and Rajarajacholan, U. and Soh, J. and Kim, T. S. and Thalappilly, S. and Sensen, C. W. and Riabowol, K. ",
    Title="{{L}inc{R}{N}{A}-p21 acts as a mediator of {I}{N}{G}1b-induced apoptosis}",
    Journal="Cell Death Dis",
    Year="2015",
    Volume="6",
    Pages="e1668",
    Abstract={ING1b is a tumor suppressor that affects transcription, cell cycle control and apoptosis. ING1b is deregulated in disease, and its activity is closely linked to that of p53. In addition to regulating protein-coding genes, we found that ING1b also influences the expression of large intergenic non-coding RNAs (lincRNAs). In particular, lincRNA-p21 was significantly induced after DNA-damage stress or by ING1b overexpression. Furthermore, lincRNA-p21 expression in response to DNA damage was significantly attenuated in cells lacking ING1b. LincRNA-p21 is also a target of p53 and can trigger apoptosis in mouse cell models. We found that this function of lincRNA-p21 is conserved in human cell models. Moreover, ING1b and p53 could function independently to influence lincRNA-p21 expression. However, their effects become more additive under conditions of stress. In particular, ING1b regulates lincRNA-p21 levels by binding to its promoter and is required for induction of lincRNA-p21 by p53. The ability of ING1b to cause apoptosis is also impaired in the absence of lincRNA-p21. Surprisingly, deletion of the ING1b plant homeodomain, which allows it to bind histones and regulate chromatin structure, did not alter regulation of lincRNA-p21. Our findings suggest that ING1b induces lincRNA-p21 expression independently of histone 3 lysine 4 trimethylation mark recognition and that lincRNA-p21 functions downstream of ING1b. Thus, regulation at the level of lincRNA-p21 may represent the point at which ING1b and p53 pathways converge to induce apoptosis under specific stress conditions.},
    Note={[PubMed Central:\href{http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4385912}{PMC4385912}] [DOI:\href{http://dx.doi.org/10.1038/cddis.2015.15}{10.1038/cddis.2015.15}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/25741593}{25741593}] }
    }
  • T. E. Parsons, C. M. Downey, F. R. Jirik, B. Hallgrimsson, and H. A. Jamniczky, “Mind the Gap: Genetic Manipulation of Basicranial Growth within Synchondroses Modulates Calvarial and Facial Shape in Mice through Epigenetic Interactions,” Plos one, vol. 10, iss. 2, p. e0118355, 2015.
    [Bibtex]
    @Article{pmid25692674,
    Author="Parsons, T. E. and Downey, C. M. and Jirik, F. R. and Hallgrimsson, B. and Jamniczky, H. A. ",
    Title="{{M}ind the {G}ap: {G}enetic {M}anipulation of {B}asicranial {G}rowth within {S}ynchondroses {M}odulates {C}alvarial and {F}acial {S}hape in {M}ice through {E}pigenetic {I}nteractions}",
    Journal="PLoS ONE",
    Year="2015",
    Volume="10",
    Number="2",
    Pages="e0118355",
    Abstract={Phenotypic integration patterns in the mammalian skull have long been a focus of intense interest as a result of their suspected influence on the trajectory of hominid evolution. Here we test the hypothesis that perturbation of cartilage growth, which directly affects only the chondrocranium during development, will produce coordinated shape changes in the adult calvarium and face regardless of mechanism. Using two murine models of cartilage undergrowth that target two very different mechanisms, we show that strong reduction in cartilage growth produces a short, wide, and more flexed cranial base. This in turn produces a short, wide face in both models. Cranial base and face are already correlated early in ontogeny, and the relationship between these modules gains structure through postnatal growth and development. These results provide further evidence that there exist physical interactions between developing parts of the phenotype that produce variation at a distance from the actual locus upon which a particular selective pressure is acting. Phenotypic changes observed over the course of evolution may not all require adaptationist explanations; rather, it is likely that a substantial portion of observed phenotypic variation over the history of a clade is not directly adaptive but rather a secondary consequence of some local response to selection.},
    Note={[PubMed Central:\href{http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334972}{PMC4334972}] [DOI:\href{http://dx.doi.org/10.1371/journal.pone.0118355}{10.1371/journal.pone.0118355}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/25692674}{25692674}] }
    }
  • Nabbi A., Almami A., Thakur S., Suzuki K., D. Boland, Bismar T., and K. Riabowol, “ING3 protein expression profiling in normal human tissues suggest its role in cellular growth and self-renewal,” European journal of cell biology, 2015.
    [Bibtex]
    @Article{EJCB,
    Author="Nabbi, A., and Almami, A., and Thakur S., and Suzuki, K., and Boland, D. and Bismar, T., and Riabowol, K.",
    Title="{ING3 protein expression profiling in normal human tissues suggest its role in cellular growth and self-renewal}",
    Journal="European Journal of Cell Biology",
    Year="2015",
    Pages=" ",
    Month="March",
    Abstract={Members of the INhibitor of Growth (ING) family of proteins act as readers of the epigenetic code through specific recognition of the trimethylated form of lysine 4 of histone H3 (H3K4Me3) by their plant homeodomains. The founding member of the family, ING1, was initially identified as a tumor suppressor with altered regulation in a variety of cancer types. While alterations in ING1 and ING4 levels have been reported in a variety of cancer types, little is known regarding ING3 protein levels in normal or transformed cells due to a lack of reliable immunological tools. In this study we present the characterization of a new monoclonal antibody we have developed against ING3 that specifically recognizes human and mouse ING3. The antibody works in western blots, immunofluorescence, immunoprecipitation and immunohistochemistry. Using this antibody we show that ING3 is most highly expressed in small intestine, bone marrow and epidermis, tissues in which cells undergo rapid proliferation and renewal. Consistent with this observation we show that ING3 is expressed at significantly higher levels in proliferating versus quiescent epithelial cells. These data suggest that ING3 levels may serve as a surrogate for growth rate, and suggest possible roles for ING3 in growth and self renewal and related diseases such as cancer.},
    Note={[DOI:\href{http://doi:10.1016/j.ejcb.2015.03.002}{10.1016/j.ejcb.2015.03.002}] [PubMed:\href{}{}] }
    }
  • G. A. Metz, J. W. Ng, I. Kovalchuk, and D. M. Olson, “Ancestral experience as a game changer in stress vulnerability and disease outcomes,” Bioessays, 2015.
    [Bibtex]
    @Article{pmid25759985,
    Author="Metz, G. A. and Ng, J. W. and Kovalchuk, I. and Olson, D. M. ",
    Title="{{A}ncestral experience as a game changer in stress vulnerability and disease outcomes}",
    Journal="Bioessays",
    Year="2015",
    Pages=" ",
    Month="Mar",
    Abstract={Stress is one of the most powerful experiences to influence health and disease. Through epigenetic mechanisms, stress may generate a footprint that propagates to subsequent generations. Programming by prenatal stress or adverse experience in parents, grandparents, or earlier generations may thus be a critical determinant of lifetime health trajectories. Changes in regulation of microRNAs (miRNAs) by stress may enhance the vulnerability to certain pathogenic factors. This review explores the hypothesis that miRNAs represent stress-responsive elements in epigenetic regulation that are potentially heritable. Recent findings suggest that miRNAs are key players linking adverse early environments or ancestral stress with disease risk, thus they represent useful predictive disease biomarkers. Since miRNA signatures of disease are potentially heritable, big data management platforms will be vital to harness multi-generational information and capture succinct yet potent biomarkers capable of directing preventative treatments. This feature would offer a unique window of opportunity to advance personalized medicine.},
    Note={[DOI:\href{http://dx.doi.org/10.1002/bies.201400217}{10.1002/bies.201400217}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/25759985}{25759985}] }
    }
  • R. Mychasiuk, H. Hehar, I. Ma, and M. J. Esser, “Dietary intake alters behavioral recovery and gene expression profiles in the brain of juvenile rats that have experienced a concussion,” Front behav neurosci, vol. 9, p. 17, 2015.
    [Bibtex]
    @Article{pmid25698949,
    Author="Mychasiuk, R. and Hehar, H. and Ma, I. and Esser, M. J. ",
    Title="{{D}ietary intake alters behavioral recovery and gene expression profiles in the brain of juvenile rats that have experienced a concussion}",
    Journal="Front Behav Neurosci",
    Year="2015",
    Volume="9",
    Pages="17",
    Abstract={Concussion and mild traumatic brain injury (mTBI) research has made minimal progress diagnosing who will suffer from lingering symptomology or generating effective treatment strategies. Research demonstrates that dietary intake affects many biological systems including brain and neurological health. This study determined if exposure to a high fat diet (HFD) or caloric restriction (CR) altered post-concussion susceptibility or resiliency using a rodent model of pediatric concussion. Rats were maintained on HFD, CR, or standard diet (STD) throughout life (including the prenatal period and weaning). At postnatal day 30, male and female rats experienced a concussion or a sham injury which was followed by 17 days of testing. Prefrontal cortex and hippocampus tissue was collected for molecular profiling. Gene expression changes in BDNF, CREB, DNMT1, FGF-2, IGF1, LEP, PGC-1α, SIRT1, Tau, and TERT were analyzed with respect to injury and diet. Analysis of telomere length (TL) using peripheral skin cells and brain tissue found that TL in skin significantly correlated with TL in brain tissue and TL was affected by dietary intake and injury status. With respect to mTBI outcomes, diet was correlated with recovery as animals on the HFD often displayed poorer performance than animals on the CR diet. Molecular analysis demonstrated that diet induced epigenetic changes that can be associated with differences in individual predisposition and resiliency to post-concussion syndrome.},
    Note={[DOI:\href{http://dx.doi.org/10.3389/fnbeh.2015.00017}{10.3389/fnbeh.2015.00017}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/25698949}{25698949}] }
    }
  • B. Kolb and R. Gibb, “Plasticity in the prefrontal cortex of adult rats,” Front cell neurosci, vol. 9, p. 15, 2015.
    [Bibtex]
    @Article{pmid25691857,
    Author="Kolb, B. and Gibb, R. ",
    Title="{{P}lasticity in the prefrontal cortex of adult rats}",
    Journal="Front Cell Neurosci",
    Year="2015",
    Volume="9",
    Pages="15",
    Abstract={We review the plastic changes of the prefrontal cortex of the rat in response to a wide range of experiences including sensory and motor experience, gonadal hormones, psychoactive drugs, learning tasks, stress, social experience, metaplastic experiences, and brain injury. Our focus is on synaptic changes (dendritic morphology and spine density) in pyramidal neurons and the relationship to behavioral changes. The most general conclusion we can reach is that the prefrontal cortex is extremely plastic and that the medial and orbital prefrontal regions frequently respond very differently to the same experience in the same brain and the rules that govern prefrontal plasticity appear to differ for those of other cortical regions.},
    Note={[PubMed Central:\href{http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4315042}{PMC4315042}] [DOI:\href{http://dx.doi.org/10.3389/fncel.2015.00015}{10.3389/fncel.2015.00015}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/25691857}{25691857}] }
    }
  • [DOI] A. Bilichak, Y. Ilnytskyy, R. Woycicki, N. Kepeshchuk, D. Fogen, and I. Kovalchuk, “The elucidation of stress memory inheritance in brassica rapa plants,” Frontiers in plant science, vol. 6, iss. 5, 2015.
    [Bibtex]
    @ARTICLE{10.3389/fpls.2015.00005,
    AUTHOR={Bilichak, Andriy and Ilnytskyy, Yaroslav and Woycicki, Rafal and Kepeshchuk, Nina and Fogen, Dawson and Kovalchuk, Igor},
    TITLE={THE ELUCIDATION OF STRESS MEMORY INHERITANCE IN BRASSICA RAPA PLANTS},
    JOURNAL={Frontiers in Plant Science},
    VOLUME={6},
    YEAR={2015},
    NUMBER={5},
    URL={http://www.frontiersin.org/plant_genetics_and_genomics/10.3389/fpls.2015.00005/abstract},
    DOI={10.3389/fpls.2015.00005},
    ISSN={1664-462X} ,
    ABSTRACT={Plants are able to maintain the memory of stress exposure throughout their ontogenesis and faithfully propagate it into the next generation. Recent evidence argues for the epigenetic nature of this phenomenon. Small RNAs (smRNAs) are one of the vital epigenetic factors because they can both affect gene expression at the place of their generation and maintain non-cell-autonomous gene regulation. Here, we have made an attempt to decipher the contribution of smRNAs to the heat-shock-induced transgenerational inheritance in Brassica rapa plants using sequencing technology. To do this, we have generated comprehensive profiles of a transcriptome and a small RNAome (smRNAome) from somatic and reproductive tissues of stressed plants and their untreated progeny. We have demonstrated that the highest tissue-specific alterations in the transcriptome and smRNAome profile are detected in tissues that were not directly exposed to stress, namely, in the endosperm and pollen. Importantly, we have revealed that the progeny of stressed plants exhibit the highest fluctuations at the smRNAome level but not at the transcriptome level. Additionally, we have uncovered the existence of heat-inducible and transgenerationally transmitted tRNA-derived small RNA fragments in plants. Finally, we suggest that miR168 and braAGO1 are involved in the stress-induced transgenerational inheritance in plants.}}
  • C. J. Billington, B. Schmidt, R. S. Marcucio, B. Hallgrimsson, R. Gopalakrishnan, and A. Petryk, “Impact of retinoic acid exposure on midfacial shape variation and manifestation of holoprosencephaly in Twsg1 mutant mice,” Dis model mech, vol. 8, iss. 2, pp. 139-146, 2015.
    [Bibtex]
    @Article{pmid25468951,
    Author="Billington, C. J. and Schmidt, B. and Marcucio, R. S. and Hallgrimsson, B. and Gopalakrishnan, R. and Petryk, A. ",
    Title="{{I}mpact of retinoic acid exposure on midfacial shape variation and manifestation of holoprosencephaly in {T}wsg1 mutant mice}",
    Journal="Dis Model Mech",
    Year="2015",
    Volume="8",
    Number="2",
    Pages="139--146",
    Month="Feb",
    Abstract={Holoprosencephaly (HPE) is a developmental anomaly characterized by inadequate or absent midline division of the embryonic forebrain and midline facial defects. It is believed that interactions between genes and the environment play a role in the widely variable penetrance and expressivity of HPE, although direct investigation of such effects has been limited. The goal of this study was to examine whether mice carrying a mutation in a gene encoding the bone morphogenetic protein (BMP) antagonist twisted gastrulation (Twsg1), which is associated with a low penetrance of HPE, are sensitized to retinoic acid (RA) teratogenesis. Pregnant Twsg1(+/-) dams were treated by gavage with a low dose of all-trans RA (3.75 mg/kg of body weight). Embryos were analyzed between embryonic day (E)9.5 and E11.5 by microscopy and geometric morphometric analysis by micro-computed tomography. P19 embryonal carcinoma cells were used to examine potential mechanisms mediating the combined effects of increased BMP and retinoid signaling. Although only 7% of wild-type embryos exposed to RA showed overt HPE or neural tube defects (NTDs), 100% of Twsg1(-/-) mutants exposed to RA manifested severe HPE compared to 17% without RA. Remarkably, up to 30% of Twsg1(+/-) mutants also showed HPE (23%) or NTDs (7%). The majority of shape variation among Twsg1(+/-) mutants was associated with narrowing of the midface. In P19 cells, RA induced the expression of Bmp2, acted in concert with BMP2 to increase p53 expression, caspase activation and oxidative stress. This study provides direct evidence for modifying effects of the environment in a genetic mouse model carrying a predisposing mutation for HPE in the Twsg1 gene. Further study of the mechanisms underlying these gene-environment interactions in vivo will contribute to better understanding of the pathogenesis of birth defects and present an opportunity to explore potential preventive interventions.},
    Note={[DOI:\href{http://dx.doi.org/10.1242/dmm.018275}{10.1242/dmm.018275}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/25468951}{25468951}] }
    }
  • I. Skelin, M. A. Needham, L. M. Molina, G. A. Metz, and A. J. Gruber, “Multigenerational prenatal stress increases the coherence of brain signaling among cortico-striatal-limbic circuits in adult rats,” Neuroscience, vol. 289C, pp. 270-278, 2015.
    [Bibtex]
    @Article{pmid25595989,
    Author="Skelin, I. and Needham, M. A. and Molina, L. M. and Metz, G. A. and Gruber, A. J. ",
    Title="{{M}ultigenerational prenatal stress increases the coherence of brain signaling among cortico-striatal-limbic circuits in adult rats}",
    Journal="Neuroscience",
    Year="2015",
    Volume="289C",
    Pages="270--278",
    Month="Jan",
    Abstract={Prenatal stress (PNS) is a significant risk factor for the development of psychopathology in adulthood such as anxiety, depression, schizophrenia and addiction. Animal models of PNS resemble many of the effects of PNS on humans and provide a means to study the accumulated effects of PNS over several generations on brain function. Here, we examined how mild PNS delivered during the third week in utero over four consecutive generations affects behavioral flexibility and functional signaling among cortical and limbic structures. These multi-generational prenatally stressed (MGPNS) rats were not impaired on an odor-cued reversal learning task as compared to control animals. Unilateral field potential (FP) recordings from the medial prefrontal cortex, basolateral amygdala, ventral hippocampus, and striatal territories revealed widespread differences in brain signaling between these groups during the odor sampling phase of the task. The FP power was significantly lower in most structures across most frequency bands in MGPNS animals, and the relative increase in power from baseline during the task was lower for the beta band (12-30Hz) in MGPNS animals as compared to controls. The coherence of FPs between brain regions, however, was much higher in MGPNS animals among all structures and for most frequency bands. We propose that this pattern of changes in brain signaling reflects a simplification of network processing, which is consistent with reports of reduced spine density and dendritic complexity in the brains of animals receiving PNS. Our data support the proposal that recurrent ancestral stress leads to adaptations in the brain, and that these may confer adaptive behavior in some circumstances as compared to single-generation PNS.},
    Note={[DOI:\href{http://dx.doi.org/10.1016/j.neuroscience.2015.01.009}{10.1016/j.neuroscience.2015.01.009}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/25595989}{25595989}] }
    }
  • C. Sidler, D. Li, O. Kovalchuk, and I. Kovalchuk, “Development-Dependent Expression of DNA Repair Genes and Epigenetic Regulators in Arabidopsis Plants Exposed to Ionizing Radiation,” Radiat. res., 2015.
    [Bibtex]
    @Article{pmid25594540,
    Author="Sidler, C. and Li, D. and Kovalchuk, O. and Kovalchuk, I. ",
    Title="{{D}evelopment-{D}ependent {E}xpression of {D}{N}{A} {R}epair {G}enes and {E}pigenetic {R}egulators in {A}rabidopsis {P}lants {E}xposed to {I}onizing {R}adiation}",
    Journal="Radiat. Res.",
    Year="2015",
    Pages=" ",
    Month="Jan",
    Abstract={Both plant senescence and plant response to ionizing radiation involve changes in gene expression and epigenetic profiles, that rely on the formation of reactive oxygen species. However, how the developmental stage of a plant affects its response to ionizing radiation has not been extensively studied. In this study, our experiments showed that exposure to low (10 Gy) and high (100 Gy) doses of ionizing radiation causes developmental delays in plants that may result in reduced biomass or even death of the organism. In particular, 20-day-old plants, which are in the process of transitioning to reproductive growth, showed a distinct response to irradiation compared to 10- or 30-day-old irradiated plants that affects the expression of DNA repair genes. Specifically, we found that the expression of mismatch repair genes was increased in 20-day-old plants, while RAD51 was increased in 10- and 30-day-old plants. Furthermore, we found increased expression of MET1, CMT3 and SUVH5 epigenetic regulators that paralleled decreased ONSEN transcript levels in 20-day-old irradiated plants. These findings suggest that plants exposed during early reproductive growth exhibit a tighter control over genome stability in response to ionizing irradiation compared to plants irradiated at other developmental stages.},
    Note={[DOI:\href{http://dx.doi.org/10.1667/RR13840.1}{10.1667/RR13840.1}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/25594540}{25594540}] }
    }
  • R. Mychasiuk, H. Hehar, I. Ma, B. Kolb, and M. J. Esser, “The development of lasting impairments: a mild pediatric brain injury alters gene expression, dendritic morphology, and synaptic connectivity in the prefrontal cortex of rats,” Neuroscience, vol. 288, pp. 145-155, 2015.
    [Bibtex]
    @ARTICLE{Mychasiuk2015145,
    author={Mychasiuk, R. and Hehar, H. and Ma, I. and Kolb, B. and Esser, M.J.},
    title={The development of lasting impairments: A mild pediatric brain injury alters gene expression, dendritic morphology, and synaptic connectivity in the prefrontal cortex of rats},
    journal={Neuroscience},
    year={2015},
    volume={288},
    pages={145-155},
    note={cited By 0},
    url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84921502321&partnerID=40&md5=4c0e721eca932b6942e71f7b771be1df},
    document_type={Article},
    source={Scopus},
    }
  • C. J. Billington, B. Schmidt, R. S. Marcucio, B. Hallgrimsson, R. Gopalakrishnan, and A. Petryk, “Impact of retinoic acid exposure on midfacial shape variation and manifestation of holoprosencephaly in Twsg1 mutant mice,” Dis model mech, vol. 8, iss. 2, pp. 139-146, 2015.
    [Bibtex]
    @Article{pmid25468951,
    Author="Billington, C. J. and Schmidt, B. and Marcucio, R. S. and Hallgrimsson, B. and Gopalakrishnan, R. and Petryk, A. ",
    Title="{{I}mpact of retinoic acid exposure on midfacial shape variation and manifestation of holoprosencephaly in {T}wsg1 mutant mice}",
    Journal="Dis Model Mech",
    Year="2015",
    Volume="8",
    Number="2",
    Pages="139--146",
    Month="Feb",
    Abstract={Holoprosencephaly (HPE) is a developmental anomaly characterized by inadequate or absent midline division of the embryonic forebrain and midline facial defects. It is believed that interactions between genes and the environment play a role in the widely variable penetrance and expressivity of HPE, although direct investigation of such effects has been limited. The goal of this study was to examine whether mice carrying a mutation in a gene encoding the bone morphogenetic protein (BMP) antagonist twisted gastrulation (Twsg1), which is associated with a low penetrance of HPE, are sensitized to retinoic acid (RA) teratogenesis. Pregnant Twsg1(+/-) dams were treated by gavage with a low dose of all-trans RA (3.75 mg/kg of body weight). Embryos were analyzed between embryonic day (E)9.5 and E11.5 by microscopy and geometric morphometric analysis by micro-computed tomography. P19 embryonal carcinoma cells were used to examine potential mechanisms mediating the combined effects of increased BMP and retinoid signaling. Although only 7% of wild-type embryos exposed to RA showed overt HPE or neural tube defects (NTDs), 100% of Twsg1(-/-) mutants exposed to RA manifested severe HPE compared to 17% without RA. Remarkably, up to 30% of Twsg1(+/-) mutants also showed HPE (23%) or NTDs (7%). The majority of shape variation among Twsg1(+/-) mutants was associated with narrowing of the midface. In P19 cells, RA induced the expression of Bmp2, acted in concert with BMP2 to increase p53 expression, caspase activation and oxidative stress. This study provides direct evidence for modifying effects of the environment in a genetic mouse model carrying a predisposing mutation for HPE in the Twsg1 gene. Further study of the mechanisms underlying these gene-environment interactions in vivo will contribute to better understanding of the pathogenesis of birth defects and present an opportunity to explore potential preventive interventions.},
    Note={[DOI:\href{http://dx.doi.org/10.1242/dmm.018275}{10.1242/dmm.018275}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/25468951}{25468951}] }
    }
  • [DOI] O. Babenko, I. Kovalchuk, and G. A. Metz, “Stress-induced perinatal and transgenerational epigenetic programming of brain development and mental health,” Neuroscience and biobehavioral reviews, vol. 48, pp. 70-91, 2015.
    [Bibtex]
    @article{babenko_stress-induced_2015,
    abstract = {Research efforts during the past decades have provided intriguing evidence suggesting that stressful experiences during pregnancy exert long-term consequences on the future mental wellbeing of both the mother and her baby. Recent human epidemiological and animal studies indicate that stressful experiences in utero or during early life may increase the risk of neurological and psychiatric disorders, arguably via altered epigenetic regulation. Epigenetic mechanisms, such as {miRNA} expression, {DNA} methylation, and histone modifications are prone to changes in response to stressful experiences and hostile environmental factors. Altered epigenetic regulation may potentially influence fetal endocrine programming and brain development across several generations. Only recently, however, more attention has been paid to possible transgenerational effects of stress. In this review we discuss the evidence of transgenerational epigenetic inheritance of stress exposure in human studies and animal models. We highlight the complex interplay between prenatal stress exposure, associated changes in {miRNA} expression and {DNA} methylation in placenta and brain and possible links to greater risks of schizophrenia, attention deficit hyperactivity disorder, autism, anxiety- or depression-related disorders later in life. Based on existing evidence, we propose that prenatal stress, through the generation of epigenetic alterations, becomes one of the most powerful influences on mental health in later life. The consideration of ancestral and prenatal stress effects on lifetime health trajectories is critical for improving strategies that support healthy development and successful aging.},
    author = {O. Babenko and I. Kovalchuk and G.A. Metz},
    citeulike-article-id = {13477168},
    citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.neubiorev.2014.11.013},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84913580377\&\#38;partnerID=40\&\#38;md5=25d7bf1c606ef4c61a34a2595c9bc6f5},
    doi = {10.1016/j.neubiorev.2014.11.013},
    journal = {Neuroscience and Biobehavioral Reviews},
    keywords = {allele, analysis, anxiety, attention, autism, brain, cell, cohort, deficit, depression, development, diet, disease, disorder, dna, domain, embryo, endocrine, epiallele, epigenetic, epigenetics, expression, fetal, fetus, function, genetic, health, histone, human, inheritance, malnutrition, mammal, mechanism, mental, methylation, microrna, modification, nonhuman, perinatal, period, placenta, predisposition, prenatal, programming, protein, regulatory, review, schizophrenia, sperm, stability, stress, transgenerational, *file-import-15-01-07},
    note = {cited By 0},
    pages = {70--91},
    posted-at = {2015-01-07 18:50:39},
    priority = {2},
    title = {{Stress-induced perinatal and transgenerational epigenetic programming of brain development and mental health}},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84913580377\&partnerID=40\&md5=25d7bf1c606ef4c61a34a2595c9bc6f5},
    volume = {48},
    year = {2015}
    }

2014

  • F. C. Zucchi, Y. Yao, Y. Ilnytskyy, J. C. Robbins, N. Soltanpour, I. Kovalchuk, O. Kovalchuk, and G. A. Metz, “Lifetime stress cumulatively programs brain transcriptome and impedes stroke recovery: benefit of sensory stimulation,” Plos one, vol. 9, iss. 3, p. e92130, 2014.
    [Bibtex]
    @Article{pmid24651125,
    Author="Zucchi, F. C. and Yao, Y. and Ilnytskyy, Y. and Robbins, J. C. and Soltanpour, N. and Kovalchuk, I. and Kovalchuk, O. and Metz, G. A. ",
    Title="{{L}ifetime stress cumulatively programs brain transcriptome and impedes stroke recovery: benefit of sensory stimulation}",
    Journal="PLoS ONE",
    Year="2014",
    Volume="9",
    Number="3",
    Pages="e92130",
    Abstract={Prenatal stress (PS) represents a critical variable affecting lifetime health trajectories, metabolic and vascular functions. Beneficial experiences may attenuate the effects of PS and its programming of health outcomes in later life. Here we investigated in a rat model (1) if PS modulates recovery following cortical ischemia in adulthood; (2) if a second hit by adult stress (AS) exaggerates stress responses and ischemic damage; and (3) if tactile stimulation (TS) attenuates the cumulative effects of PS and AS. Prenatally stressed and non-stressed adult male rats underwent focal ischemic motor cortex lesion and were tested in skilled reaching and skilled walking tasks. Two groups of rats experienced recurrent restraint stress in adulthood and one of these groups also underwent daily TS therapy. Animals that experienced both PS and AS displayed the most severe motor disabilities after lesion. By contrast, TS promoted recovery from ischemic lesion and reduced hypothalamic-pituitary-adrenal axis activity. The data also showed that cumulative effects of adverse and beneficial lifespan experiences interact with disease outcomes and brain plasticity through the modulation of gene expression. Microarray analysis of the lesion motor cortex revealed that cumulative PS and AS interact with genes related to growth factors and transcription factors, which were not affected by PS or lesion alone. TS in PS+AS animals reverted these changes, suggesting a critical role for these factors in activity-dependent motor cortical reorganization after ischemic lesion. These findings suggest that beneficial experience later in life can moderate adverse consequences of early programming to improve cerebrovascular health.},
    Note={[PubMed Central:\href{http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3961295}{PMC3961295}] [DOI:\href{http://dx.doi.org/10.1371/journal.pone.0092130}{10.1371/journal.pone.0092130}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/24651125}{24651125}] }
    }
  • P. Bose, S. S. Thakur, N. T. Brockton, A. C. Klimowicz, E. Kornaga, S. C. Nakoneshny, K. T. Riabowol, and J. C. Dort, “Tumor cell apoptosis mediated by cytoplasmic ING1 is associated with improved survival in oral squamous cell carcinoma patients,” Oncotarget, vol. 5, iss. 10, pp. 3210-3219, 2014.
    [Bibtex]
    @Article{pmid24912621,
    Author="Bose, P. and Thakur, S. S. and Brockton, N. T. and Klimowicz, A. C. and Kornaga, E. and Nakoneshny, S. C. and Riabowol, K. T. and Dort, J. C. ",
    Title="{{T}umor cell apoptosis mediated by cytoplasmic {I}{N}{G}1 is associated with improved survival in oral squamous cell carcinoma patients}",
    Journal="Oncotarget",
    Year="2014",
    Volume="5",
    Number="10",
    Pages="3210--3219",
    Month="May",
    Abstract={The ING1 epigenetic regulator and tumor suppressor plays a central role in apoptosis. The Ing1 gene is functionally inactivated in many cancer types but is rarely mutated. Although most studies have implicated the major ING1 isoform, p33ING1b, in nuclear apoptotic signalling, we recently discovered a novel and potent apoptosis-inducing effect of p33ING1b translocation to the mitochondria in response to DNA damage. In the present study, we examined the impact of cytoplasmic/mitochondrial localization of p33ING1b in oral squamous cell carcinoma (OSCC) patient samples and explored the therapeutic potential of adenovirally-overexpressed p33ING1b in OSCC cell lines in combination with ionizing radiation (IR) treatment. In contrast with previous reports, we found that p33ING1b protein and mRNA levels are higher in OSCC compared to normal epithelial cells. In OSCC patient samples, higher levels of intra-tumoral cytoplasmic p33ING1b correlated with increased apoptotic markers and significantly better patient survival. This association was strongest in patients who received post-operative radiotherapy. IR treatment induced p33ING1b translocation to the mitochondria and adenoviral-p33ING1b synergized with IR to kill OSCC cells. Our results identify a novel functional relationship between cytoplasmic p33ING1b and patient survival and highlight the potential for the use of p33ING1b as a therapeutic agent in combination with adjuvant radiotherapy in OSCC.},
    Note={[PubMed Central:\href{http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4102804}{PMC4102804}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/24912621}{24912621}] }
    }
  • S. Satpathy, C. Guerillon, T. S. Kim, N. Bigot, S. Thakur, S. Bonni, K. Riabowol, and R. Pedeux, “SUMOylation of the ING1b tumor suppressor regulates gene transcription,” Carcinogenesis, vol. 35, iss. 10, pp. 2214-2223, 2014.
    [Bibtex]
    @Article{pmid24903338,
    Author="Satpathy, S. and Guerillon, C. and Kim, T. S. and Bigot, N. and Thakur, S. and Bonni, S. and Riabowol, K. and Pedeux, R. ",
    Title="{{S}{U}{M}{O}ylation of the {I}{N}{G}1b tumor suppressor regulates gene transcription}",
    Journal="Carcinogenesis",
    Year="2014",
    Volume="35",
    Number="10",
    Pages="2214--2223",
    Month="Oct",
    Abstract={The INhibitor of Growth (ING) proteins are encoded as multiple isoforms in five ING genes (ING1 -5) and act as type II tumor suppressors. They are growth inhibitory when overexpressed and are frequently mislocalized or downregulated in several forms of cancer. ING1 and ING2 are stoichiometric members of histone deacetylase complexes, whereas ING3-5 are stoichiometric components of different histone acetyltransferase complexes. The INGs target these complexes to histone marks, thus acting as epigenetic regulators. ING proteins affect angiogenesis, apoptosis, DNA repair, metastasis and senescence, but how the proteins themselves are regulated is not yet clear. Here, we find a small ubiquitin-like modification (SUMOylation) of the ING1b protein and identify lysine 193 (K193) as the preferred ING1b SUMO acceptor site. We also show that PIAS4 is the E3 SUMO ligase responsible for ING1b SUMOylation on K193. Sequence alignment reveals that the SUMO consensus site on ING1b contains a phosphorylation-dependent SUMOylation motif (PDSM) and our data indicate that the SUMOylation on K193 is enhanced by the S199D phosphomimic mutant. Using an ING1b protein mutated at the major SUMOylation site (ING1b E195A), we further demonstrate that ING1b SUMOylation regulates the binding of ING1b to the ISG15 and DGCR8 promoters, consequently regulating ISG15 and DGCR8 transcription. These results suggest a role for ING1b SUMOylation in the regulation of gene transcription.},
    Note={[PubMed Central:\href{http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4178466}{PMC4178466}] [DOI:\href{http://dx.doi.org/10.1093/carcin/bgu126}{10.1093/carcin/bgu126}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/24903338}{24903338}] }
    }
  • M. Gardner, D. Bann, L. Wiley, R. Cooper, R. Hardy, D. Nitsch, C. Martin-Ruiz, P. Shiels, A. A. Sayer, M. Barbieri, S. Bekaert, C. Bischoff, A. Brooks-Wilson, W. Chen, C. Cooper, K. Christensen, T. De Meyer, I. Deary, G. Der, A. Diez Roux, A. Fitzpatrick, A. Hajat, J. Halaschek-Wiener, S. Harris, S. C. Hunt, C. Jagger, H. S. Jeon, R. Kaplan, M. Kimura, P. Lansdorp, C. Li, T. Maeda, M. Mangino, T. S. Nawrot, P. Nilsson, K. Nordfjall, G. Paolisso, F. Ren, K. Riabowol, T. Robertson, G. Roos, J. A. Staessen, T. Spector, N. Tang, B. Unryn, P. van der Harst, J. Woo, C. Xing, M. E. Yadegarfar, J. Y. Park, N. Young, D. Kuh, T. von Zglinicki, and Y. Ben-Shlomo, “Gender and telomere length: systematic review and meta-analysis,” Exp. gerontol., vol. 51, pp. 15-27, 2014.
    [Bibtex]
    @Article{pmid24365661,
    Author="Gardner, M. and Bann, D. and Wiley, L. and Cooper, R. and Hardy, R. and Nitsch, D. and Martin-Ruiz, C. and Shiels, P. and Sayer, A. A. and Barbieri, M. and Bekaert, S. and Bischoff, C. and Brooks-Wilson, A. and Chen, W. and Cooper, C. and Christensen, K. and De Meyer, T. and Deary, I. and Der, G. and Diez Roux, A. and Fitzpatrick, A. and Hajat, A. and Halaschek-Wiener, J. and Harris, S. and Hunt, S. C. and Jagger, C. and Jeon, H. S. and Kaplan, R. and Kimura, M. and Lansdorp, P. and Li, C. and Maeda, T. and Mangino, M. and Nawrot, T. S. and Nilsson, P. and Nordfjall, K. and Paolisso, G. and Ren, F. and Riabowol, K. and Robertson, T. and Roos, G. and Staessen, J. A. and Spector, T. and Tang, N. and Unryn, B. and van der Harst, P. and Woo, J. and Xing, C. and Yadegarfar, M. E. and Park, J. Y. and Young, N. and Kuh, D. and von Zglinicki, T. and Ben-Shlomo, Y. ",
    Title="{{G}ender and telomere length: systematic review and meta-analysis}",
    Journal="Exp. Gerontol.",
    Year="2014",
    Volume="51",
    Pages="15--27",
    Month="Mar",
    Abstract={It is widely believed that females have longer telomeres than males, although results from studies have been contradictory.\\ We carried out a systematic review and meta-analyses to test the hypothesis that in humans, females have longer telomeres than males and that this association becomes stronger with increasing age. Searches were conducted in EMBASE and MEDLINE (by November 2009) and additional datasets were obtained from study investigators. Eligible observational studies measured telomeres for both females and males of any age, had a minimum sample size of 100 and included participants not part of a diseased group. We calculated summary estimates using random-effects meta-analyses. Heterogeneity between studies was investigated using sub-group analysis and meta-regression.\\ Meta-analyses from 36 cohorts (36,230 participants) showed that on average females had longer telomeres than males (standardised difference in telomere length between females and males 0.090, 95% CI 0.015, 0.166; age-adjusted). There was little evidence that these associations varied by age group (p=1.00) or cell type (p=0.29). However, the size of this difference did vary by measurement methods, with only Southern blot but neither real-time PCR nor Flow-FISH showing a significant difference. This difference was not associated with random measurement error.\\ Telomere length is longer in females than males, although this difference was not universally found in studies that did not use Southern blot methods. Further research on explanations for the methodological differences is required.},
    Note={[DOI:\href{http://dx.doi.org/10.1016/j.exger.2013.12.004}{10.1016/j.exger.2013.12.004}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/24365661}{24365661}] }
    }
  • R. Xiang, G. G. Estrella C. A. S., C. J. Fitzsimmons, Z. A. Kruk, D. A. Thomsen, R. D. L., C. T. Roberts, and S. Hiendleder, ” 97 MAGNITUDE AND SPECIFICITY OF EFFECTS OF MATERNAL AND PATERNAL GENOMES ON THE FETO-PLACENTAL UNIT,” Reproduction, fertility and development, vol. 27, iss. 1, pp. 141-141, 2014.
    [Bibtex]
    @Article{RFD12,
    Author="Xiang, R. and Estrella, C. A. S., G. G. and Fitzsimmons, C. J. and Kruk, Z A. and Thomsen, D. A. and Rutley D. L. and Roberts, C. T. and Hiendleder, S.",
    Title="{ 97 MAGNITUDE AND SPECIFICITY OF EFFECTS OF MATERNAL AND PATERNAL GENOMES ON THE FETO-PLACENTAL UNIT}",
    Journal="Reproduction, Fertility and Development",
    Year="2014",
    Volume="27",
    Number="1",
    Pages="141-141",
    Month="Dec",
    Abstract={The placenta, a major determinant of fetal growth in eutherians, facilitates maternal-fetal cross talk and mediates programming of postnatal phenotype via genetic and epigenetic mechanisms. However, magnitude and specificity of effects of maternal and paternal genomes on placental and fetal phenotype and their relationships are unclear. Using an outbred bovine intra-species model with well-defined Bos taurus taurus and Bos taurus indicus maternal and paternal genetics, we generated purebred and reciprocal cross fetuses (Animal Ethics No. S-094-2005) to dissect and quantify effects of parental genomes, fetal sex, and nongenetic maternal effects (maternal weight and post-conception maternal weight gain) on 41 gross and histomorphological feto-placental parameters. Analysis of data from 73 fetuses recovered at midgestation (Day 153) with general linear models (Xiang et al. 2014 JBMR http://dx.doi.org/10.1002/jbmr.2263) using the GLM procedure of R version 22.14 (R Development Core Team, Vienna, Austria) revealed that maternal and paternal genome combined explained the highest proportion of variation (47.2–99.5%) in 30 investigated parameters with significant (P < 0.05–0.0001) models. Fetal sex accounted for up to 32.2% (P < 0.05–0.0001) and nongenetic maternal effects for up to 25.1% (P < 0.05–0.001) of variation in 11 and 14 parameters, respectively. Partitioning of parental (epi)genome variation showed that the maternal genome predominantly contributed to variation in gross (80.3–95.7%; P < 0.05–0.0001) and histomorphological (51.5–82.1%; P < 0.05–0.0001) placental parameters, fetal weight (54.1%; P < 0.0001), and fetal organ weights (43.7–73.1%; P < 0.05–0.0001), whereas the paternal genome predominantly contributed to fetal fluids weight (73.0%; P < 0.001), umbilical cord weight (73.9%; P < 0.05) and length (73.2%; P < 0.01), and placental (69.6%; P < 0.05) and umbilical cord (83.2%; P < 0.0001) efficiency. Our finding that the maternal genome determined placental phenotype (i.e. nutrient source) and the paternal genome determined umbilical cord and fetal fluid phenotype (i.e. nutrient flow) is in line with predicted expression patterns of genomic imprinting effects by both maternal-offspring coadaptation (Wolf and Hager 2006 PLoS Biol. 4, e380) and conflict-of-interest (Moore and Haig 1991 Trends Genet 7, 45–49) hypotheses in the feto-placental unit. Furthermore, there were 4 maternal genome determined relationships between placental weights and umbilical cord phenotype (P < 0.05–0.0001) and 28 paternal genome and/or fetal sex-determined relationships between fetus-, organ- and fetal fluid weights and umbilical cord phenotype (P < 0.05–0.0001). The finding of specific relationships between placenta and fetus merging in clusters differentiated by maternal and paternal genome effects suggests the existence of (epi)genetic-regulated morphological modules within the feto-placental unit.}
    }
  • R. M. Friis and M. C. Schultz, “The timing is right,” Nat. struct. mol. biol., vol. 21, iss. 10, pp. 846-847, 2014.
    [Bibtex]
    @Article{pmid25289591,
    Author="Friis, R. M. and Schultz, M. C. ",
    Title="{{T}he timing is right}",
    Journal="Nat. Struct. Mol. Biol.",
    Year="2014",
    Volume="21",
    Number="10",
    Pages="846--847",
    Month="Oct",
    Note={[DOI:\href{http://dx.doi.org/10.1038/nsmb.2898}{10.1038/nsmb.2898}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/25289591}{25289591}] }
    }
  • B. Kolb and A. Muhammad, “Harnessing the power of neuroplasticity for intervention,” Front hum neurosci, vol. 8, p. 377, 2014.
    [Bibtex]
    @Article{pmid25018713,
    Author="Kolb, B. and Muhammad, A. ",
    Title="{{H}arnessing the power of neuroplasticity for intervention}",
    Journal="Front Hum Neurosci",
    Year="2014",
    Volume="8",
    Pages="377",
    Abstract={A fundamental property of the brain is its capacity to change with a wide variety of experiences, including injury. Although there are spontaneous reparative changes following injury, these changes are rarely sufficient to support significant functional recovery. Research on the basic principles of brain plasticity is leading to new approaches to treating the injured brain. We review factors that affect synaptic organization in the normal brain, evidence of spontaneous neuroplasticity after injury, and the evidence that factors including postinjury experience, pharmacotherapy, and cell-based therapies, can form the basis of rehabilitation strategies after brain injuries early in life and in adulthood.},
    Note={[PubMed Central:\href{http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072970}{PMC4072970}] [DOI:\href{http://dx.doi.org/10.3389/fnhum.2014.00377}{10.3389/fnhum.2014.00377}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/25018713}{25018713}] }
    }
  • K. Tsai, L. Chan, R. Gibeault, K. Conn, J. Dheekollu, J. Domsic, R. Marmorstein, L. M. Schang, and P. M. Lieberman, “Viral reprogramming of the Daxx histone H3.3 chaperone during early Epstein-Barr virus infection,” J. virol., vol. 88, iss. 24, pp. 14350-14363, 2014.
    [Bibtex]
    @Article{pmid25275136,
    Author="Tsai, K. and Chan, L. and Gibeault, R. and Conn, K. and Dheekollu, J. and Domsic, J. and Marmorstein, R. and Schang, L. M. and Lieberman, P. M. ",
    Title="{{V}iral reprogramming of the {D}axx histone {H}3.3 chaperone during early {E}pstein-{B}arr virus infection}",
    Journal="J. Virol.",
    Year="2014",
    Volume="88",
    Number="24",
    Pages="14350--14363",
    Month="Dec",
    Abstract={Host chromatin assembly can function as a barrier to viral infection. Epstein-Barr virus (EBV) establishes latent infection as chromatin-assembled episomes in which all but a few viral genes are transcriptionally silent. The factors that control chromatin assembly and guide transcription regulation during the establishment of latency are not well understood. Here, we demonstrate that the EBV tegument protein BNRF1 binds the histone H3.3 chaperone Daxx to modulate histone mobility and chromatin assembly on the EBV genome during the early stages of primary infection. We demonstrate that BNRF1 substitutes for the repressive cochaperone ATRX to form a ternary complex of BNRF1-Daxx-H3.3-H4, using coimmunoprecipitation and size-exclusion chromatography with highly purified components. FRAP (fluorescence recovery after photobleaching) assays were used to demonstrate that BNRF1 promotes global mobilization of cellular histone H3.3. Mutation of putative nucleotide binding motifs on BNRF1 attenuates the displacement of ATRX from Daxx. We also show by immunofluorescence combined with fluorescence in situ hybridization that BNRF1 is important for the dissociation of ATRX and Daxx from nuclear bodies during de novo infection of primary B lymphocytes. Virion-delivered BNRF1 suppresses Daxx-ATRX-mediated H3.3 loading on viral chromatin as measured by chromatin immunoprecipitation assays and enhances viral gene expression during early infection. We propose that EBV tegument protein BNRF1 replaces ATRX to reprogram Daxx-mediated H3.3 loading, in turn generating chromatin suitable for latent gene expression.\\ Epstein-Barr Virus (EBV) is a human herpesvirus that efficiently establishes latent infection in primary B lymphocytes. Cellular chromatin assembly plays an important role in regulating the establishment of EBV latency. We show that the EBV tegument protein BNRF1 functions to regulate chromatin assembly on the viral genome during early infection. BNRF1 alters the host cellular chromatin assembly to prevent antiviral repressive chromatin and establish chromatin structure permissive for viral gene expression and the establishment of latent infection.},
    Note={[PubMed Central:\href{http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4249116}{PMC4249116}] [DOI:\href{http://dx.doi.org/10.1128/JVI.01895-14}{10.1128/JVI.01895-14}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/25275136}{25275136}] }
    }
  • C. Ptak, J. D. Aitchison, and R. W. Wozniak, “The multifunctional nuclear pore complex: a platform for controlling gene expression,” Curr. opin. cell biol., vol. 28, pp. 46-53, 2014.
    [Bibtex]
    @Article{pmid24657998,
    Author="Ptak, C. and Aitchison, J. D. and Wozniak, R. W. ",
    Title="{{T}he multifunctional nuclear pore complex: a platform for controlling gene expression}",
    Journal="Curr. Opin. Cell Biol.",
    Year="2014",
    Volume="28",
    Pages="46--53",
    Month="Jun",
    Abstract={In addition to their established roles in nucleocytoplasmic transport, the intimate association of nuclear pore complexes (NPCs) with chromatin has long led to speculation that these structures influence peripheral chromatin structure and regulate gene expression. These ideas have their roots in morphological observations, however recent years have seen the identification of physical interactions between NPCs, chromatin, and the transcriptional machinery. Key insights into the molecular functions of specific NPC proteins have uncovered roles for these proteins in transcriptional activation and elongation, mRNA processing, as well as chromatin structure and localization. Here, we review recent studies that provide further molecular detail on the role of specific NPC components as distinct platforms for these chromatin dependent processes.},
    Note={[PubMed Central:\href{http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4061258}{PMC4061258}] [DOI:\href{http://dx.doi.org/10.1016/j.ceb.2014.02.001}{10.1016/j.ceb.2014.02.001}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/24657998}{24657998}] }
    }
  • M. K. Dyck, C. Zhou, S. Tsoi, J. Grant, W. T. Dixon, and G. R. Foxcroft, “Reproductive technologies and the porcine embryonic transcriptome,” Anim. reprod. sci., vol. 149, iss. 1-2, pp. 11-18, 2014.
    [Bibtex]
    @Article{pmid24953007,
    Author="Dyck, M. K. and Zhou, C. and Tsoi, S. and Grant, J. and Dixon, W. T. and Foxcroft, G. R. ",
    Title="{{R}eproductive technologies and the porcine embryonic transcriptome}",
    Journal="Anim. Reprod. Sci.",
    Year="2014",
    Volume="149",
    Number="1-2",
    Pages="11--18",
    Month="Sep",
    Abstract={The domestic pig is not only an economically-important livestock species, but also an increasingly recognized biomedical animal model due to its physiological similarities with humans. As a result, there is a strong interest in the factors that affect the efficient production of viable embryos and offspring in the pig using either in vivo or in vitro production methods. The application of assisted reproductive technologies (ART) has the potential to increase reproductive efficiency in livestock. These technologies include, but are not limited to: artificial insemination (AI), fixed-time AI, embryo transfer, cryopreservation of sperm/oocytes/embryos, in vitro fertilization and somatic cell nuclear transfer (cloning). However, the application of ART is much less efficient in the pig than in many other mammalian species such as cattle. Until recently, the underlying causes of these inefficiencies have been difficult to study, but advances in molecular biology techniques for studying gene expression have resulted in the availability of a variety of options for gene expression profiling such as microarrays, and next generation sequencing technologies. Capitalizing on these technologies the effects of various ARTs on the porcine embryonic transcriptome has been determined and the impact on the related biological pathways and functions been evaluated. The implications of these results on the efficiency of ARTs in swine, as well potential consequences for the developing embryo and resulting offspring, are reviewed.},
    Note={[DOI:\href{http://dx.doi.org/10.1016/j.anireprosci.2014.05.013}{10.1016/j.anireprosci.2014.05.013}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/24953007}{24953007}] }
    }
  • R. Xiang, A. M. Lee, T. Eindorf, A. Javadmanesh, M. Ghanipoor-Samami, M. Gugger, C. J. Fitzsimmons, Z. A. Kruk, W. S. Pitchford, A. J. Leviton, D. A. Thomsen, I. Beckman, G. I. Anderson, B. M. Burns, D. L. Rutley, C. J. Xian, and S. Hiendleder, “Widespread differential maternal and paternal genome effects on fetal bone phenotype at mid-gestation,” J. bone miner. res., vol. 29, iss. 11, pp. 2392-2404, 2014.
    [Bibtex]
    @Article{pmid24753181,
    Author="Xiang, R. and Lee, A. M. and Eindorf, T. and Javadmanesh, A. and Ghanipoor-Samami, M. and Gugger, M. and Fitzsimmons, C. J. and Kruk, Z. A. and Pitchford, W. S. and Leviton, A. J. and Thomsen, D. A. and Beckman, I. and Anderson, G. I. and Burns, B. M. and Rutley, D. L. and Xian, C. J. and Hiendleder, S. ",
    Title="{{W}idespread differential maternal and paternal genome effects on fetal bone phenotype at mid-gestation}",
    Journal="J. Bone Miner. Res.",
    Year="2014",
    Volume="29",
    Number="11",
    Pages="2392--2404",
    Month="Nov",
    Abstract={Parent-of-origin-dependent (epi)genetic factors are important determinants of prenatal development that program adult phenotype. However, data on magnitude and specificity of maternal and paternal genome effects on fetal bone are lacking. We used an outbred bovine model to dissect and quantify effects of parental genomes, fetal sex, and nongenetic maternal effects on the fetal skeleton and analyzed phenotypic and molecular relationships between fetal muscle and bone. Analysis of 51 bone morphometric and weight parameters from 72 fetuses recovered at day 153 gestation (54% term) identified six principal components (PC1-6) that explained 80% of the variation in skeletal parameters. Parental genomes accounted for most of the variation in bone wet weight (PC1, 72.1%), limb ossification (PC2, 99.8%), flat bone size (PC4, 99.7%), and axial skeletal growth (PC5, 96.9%). Limb length showed lesser effects of parental genomes (PC3, 40.8%) and a significant nongenetic maternal effect (gestational weight gain, 29%). Fetal sex affected bone wet weight (PC1, p < 0.0001) and limb length (PC3, p < 0.05). Partitioning of variation explained by parental genomes revealed strong maternal genome effects on bone wet weight (74.1%, p < 0.0001) and axial skeletal growth (93.5%, p < 0.001), whereas paternal genome controlled limb ossification (95.1%, p < 0.0001). Histomorphometric data revealed strong maternal genome effects on growth plate height (98.6%, p < 0.0001) and trabecular thickness (85.5%, p < 0.0001) in distal femur. Parental genome effects on fetal bone were mirrored by maternal genome effects on fetal serum 25-hydroxyvitamin D (96.9%, p < 0.001) and paternal genome effects on alkaline phosphatase (90.0%, p < 0.001) and their correlations with maternally controlled bone wet weight and paternally controlled limb ossification, respectively. Bone wet weight and flat bone size correlated positively with muscle weight (r = 0.84 and 0.77, p < 0.0001) and negatively with muscle H19 expression (r = -0.34 and -0.31, p < 0.01). Because imprinted maternally expressed H19 regulates growth factors by miRNA interference, this suggests muscle-bone interaction via epigenetic factors.},
    Note={[DOI:\href{http://dx.doi.org/10.1002/jbmr.2263}{10.1002/jbmr.2263}] [PubMed:\href{http://www.ncbnlm.nih.gov/pubmed/24753181}{24753181}] }
    }
  • S. J. Meale, J. M. Romao, M. L. He, A. V. Chaves, T. A. McAllister, and L. L. Guan, “Effect of diet on microRNA expression in ovine subcutaneous and visceral adipose tissues,” J. anim. sci., vol. 92, iss. 8, pp. 3328-3337, 2014.
    [Bibtex]
    @Article{pmid24893997,
    Author="Meale, S. J. and Romao, J. M. and He, M. L. and Chaves, A. V. and McAllister, T. A. and Guan, L. L. ",
    Title="{{E}ffect of diet on micro{R}{N}{A} expression in ovine subcutaneous and visceral adipose tissues}",
    Journal="J. Anim. Sci.",
    Year="2014",
    Volume="92",
    Number="8",
    Pages="3328--3337",
    Month="Aug",
    Abstract={Knowledge of the molecular mechanisms that regulate ovine adipogenesis is very limited. MicroRNAs (miRNA) have been reported as one of the regulatory mechanisms of adipogenesis. This study aimed to compare the expression of miRNA related to ovine adipogenesis in different adipose depots and to investigate whether their expression is affected by dietary fatty acid composition. We also investigated the role of miRNA in adipogenic gene regulation. Subcutaneous and visceral adipose tissue samples were collected at slaughter from 12 Canadian Arcott lambs fed a barley-based finishing diet where an algae meal (DHA-Gold; Schizochytrium spp.) replaced flax oil and barley grain at 0 or 3% DM (n = 6). Total RNA from each tissue was subjected to quantitative real time (qRT-) PCR analysis to determine the expression of 15 selected miRNA including 11 identified from bovine adipose tissues and 4 conserved between bovine and ovine species. MicroRNAs were differentially expressed according to diet in each tissue depot (miR-142-5p and miR-376d) in visceral and miR-142-5p, miR-92a, and miR-378 in subcutaneous adipose tissue; P ≤ 0.05) and in each tissue depot depending on diet (miR-101, miR-106, miR-136, miR-16b, miR-196a-1, miR-2368*, miR-2454, miR-296, miR-376d, miR-378, and miR-92a in both control and DHA-G diets and miR-478 in control; P ≤ 0.05). Six miRNA were subjected to functional analysis and 3 genes of interest (ACSL1, PPARα, and C/EBPα) were validated by qRT-PCR. Both diet and tissue depot affected expression levels of all 3 genes (P < 0.05). miR-101, miR-106, and miR-136 were negatively correlated with their respective predicted gene targets C/EBPα, PPARα, and ACSL1 in subcutaneous adipose tissue of lambs fed DHA-G. Yet miR-142-5p and miR-101 showed no correlation with ACSL1 or C/EBPα. The variability in expression patterns of miRNA across adipose depots reflects the tissue specific nature of adipogenic regulation. Although the examined miRNA appear to be conserved across ruminant species, our results indicate the presence of ovine specific regulatory mechanisms that can be influenced by diet.},
    Note={[DOI:\href{http://dx.doi.org/10.2527/jas.2014-7710}{10.2527/jas.2014-7710}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/24893997}{24893997}] }
    }
  • G. Liang, N. Malmuthuge, T. B. McFadden, H. Bao, P. J. Griebel, P. Stothard, and L. l. e. Guan, “Potential regulatory role of microRNAs in the development of bovine gastrointestinal tract during early life,” Plos one, vol. 9, iss. 3, p. e92592, 2014.
    [Bibtex]
    @Article{pmid24682221,
    Author="Liang, G. and Malmuthuge, N. and McFadden, T. B. and Bao, H. and Griebel, P. J. and Stothard, P. and Guan, l. e. L. ",
    Title="{{P}otential regulatory role of micro{R}{N}{A}s in the development of bovine gastrointestinal tract during early life}",
    Journal="PLoS ONE",
    Year="2014",
    Volume="9",
    Number="3",
    Pages="e92592",
    Abstract={This study aimed to investigate the potential regulatory role of miRNAs in the development of gastrointestinal tract (GIT) during the early life of dairy calves. Rumen and small intestinal (mid-jejunum and ileum) tissue samples were collected from newborn (30 min after birth; n = 3), 7-day-old (n = 6), 21-day-old (n = 6), and 42-day-old (n = 6) dairy calves. The miRNA profiling was performed using Illumina RNA-sequencing and the temporal and regional differentially expressed miRNAs were further validated using qRT-PCR. Analysis of 16S rRNA gene copy numbers was used to quantify total bacteria, Bifidobacterium and Lactobacillus species. The expression of miR-143 was abundant in all three gut regions, at all time points and it targets genes involved primarily in the proliferation of connective tissue cells and muscle cells, suggesting a role in regulating rapid tissue development during the early life of calves. The expression of miR-146, miR-191, miR-33, miR-7, miR-99/100, miR-486, miR-145, miR-196 and miR-211 displayed significant temporal differences (FDR <0.05), while miR-192/215, miR-194, miR-196, miR-205 and miR-31 revealed significant regional differences (FDR <0.05). The expression levels of miR-15/16, miR-29 and miR-196 were positively correlated with the copy numbers of 16S rRNA gene of Bifidobacterium or Lactobacillus species or both (P<0.05). Functional analysis using Ingenuity Pathway Analysis identified the above mentioned differentially expressed miRNAs as potential regulators of gut tissue cell proliferation and differentiation. The bacterial density-associated miRNAs were identified as modulators of the development of lymphoid tissues (miR-196), maturation of dendritic cells (miR-29) and development of immune cells (miR-15/16). The present study revealed temporal and regional changes in miRNA expression and a correlation between miRNA expression and microbial population in the GIT during the early life, which provides further evidence for another mechanism by which host-microbial interactions play a role in regulating gut development.},
    Note={[PubMed Central:\href{http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3969364}{PMC3969364}] [DOI:\href{http://dx.doi.org/10.1371/journal.pone.0092592}{10.1371/journal.pone.0092592}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/24682221}{24682221}] }
    }
  • G. Liang, N. Malmuthuge, L. L. Guan, and P. Griebel, “Model systems to analyze the role of miRNAs and commensal microflora in bovine mucosal immune system development,” Mol. immunol., 2014.
    [Bibtex]
    @Article{pmid25467799,
    Author="Liang, G. and Malmuthuge, N. and Guan, L. L. and Griebel, P. ",
    Title="{{M}odel systems to analyze the role of mi{R}{N}{A}s and commensal microflora in bovine mucosal immune system development}",
    Journal="Mol. Immunol.",
    Year="2014",
    Pages=" ",
    Month="Nov",
    Abstract={Information is rapidly accumulating regarding the role of miRNAs as key regulators of immune system development and function. It is also increasingly evident that miRNAs play an important role in host-pathogen interactions through regulation of both innate and acquired immune responses. Little is known, however, about the specific role of miRNAs in regulating normal development of the mucosal immune system, especially during the neonatal period. Furthermore, there is limited knowledge regarding the possible role the commensal microbiome may play in regulating mucosal miRNAs expression, although evidence is emerging that a variety of enteric pathogens influence miRNA expression. The current review focuses on recent information that miRNAs play an important role in regulating early development of the bovine mucosal immune system. A possible role for the commensal microbiome in regulating mucosal development by altering miRNA expression is also discussed. Finally, we explore the potential advantages of using the newborn calf as a model to determine how interactions between developmental programming, maternal factors in colostrum, and colonization of the gastrointestinal tract by commensal bacteria may alter mucosal miRNA expression and immune development. Identifying the key factors that regulate mucosal miRNA expression is critical for understanding how the balance between protective immunity and inflammation is maintained to ensure optimal gastrointestinal tract function and health of the whole organism.},
    Note={[DOI:\href{http://dx.doi.org/10.1016/j.molimm.2014.10.014}{10.1016/j.molimm.2014.10.014}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/25467799}{25467799}] }
    }
  • R. M. Friis, J. P. Glaves, T. Huan, L. Li, B. D. Sykes, and M. C. Schultz, “Rewiring AMPK and mitochondrial retrograde signaling for metabolic control of aging and histone acetylation in respiratory-defective cells,” Cell rep, vol. 7, iss. 2, pp. 565-574, 2014.
    [Bibtex]
    @Article{pmid24726357,
    Author="Friis, R. M. and Glaves, J. P. and Huan, T. and Li, L. and Sykes, B. D. and Schultz, M. C. ",
    Title="{{R}ewiring {A}{M}{P}{K} and mitochondrial retrograde signaling for metabolic control of aging and histone acetylation in respiratory-defective cells}",
    Journal="Cell Rep",
    Year="2014",
    Volume="7",
    Number="2",
    Pages="565--574",
    Month="Apr",
    Abstract={Abnormal respiratory metabolism plays a role in numerous human disorders. We find that regulation of overall histone acetylation is perturbed in respiratory-incompetent (ρ(0)) yeast. Because histone acetylation is highly sensitive to acetyl-coenzyme A (acetyl-CoA) availability, we sought interventions that suppress this ρ(0) phenotype through reprogramming metabolism. Nutritional intervention studies led to the discovery that genetic coactivation of the mitochondrion-to-nucleus retrograde (RTG) response and the AMPK (Snf1) pathway prevents abnormal histone deacetylation in ρ(0) cells. Metabolic profiling of signaling mutants uncovered links between chromatin-dependent phenotypes of ρ(0) cells and metabolism of ATP, acetyl-CoA, glutathione, branched-chain amino acids, and the storage carbohydrate trehalose. Importantly, RTG/AMPK activation reprograms energy metabolism to increase the supply of acetyl-CoA to lysine acetyltransferases and extend the chronological lifespan of ρ(0) cells. Our results strengthen the framework for rational design of nutrient supplementation schemes and drug-discovery initiatives aimed at mimicking the therapeutic benefits of dietary interventions.},
    Note={[DOI:\href{http://dx.doi.org/10.1016/j.celrep.2014.03.029}{10.1016/j.celrep.2014.03.029}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/24726357}{24726357}] }
    }
  • L. Radan, C. S. Hughes, J. H. Teichroeb, F. M. Vieira Zamora, M. Jewer, L. M. Postovit, and D. H. Betts, “Microenvironmental regulation of telomerase isoforms in human embryonic stem cells,” Stem cells dev., vol. 23, iss. 17, pp. 2046-2066, 2014.
    [Bibtex]
    @Article{pmid24749509,
    Author="Radan, L. and Hughes, C. S. and Teichroeb, J. H. and Vieira Zamora, F. M. and Jewer, M. and Postovit, L. M. and Betts, D. H. ",
    Title="{{M}icroenvironmental regulation of telomerase isoforms in human embryonic stem cells}",
    Journal="Stem Cells Dev.",
    Year="2014",
    Volume="23",
    Number="17",
    Pages="2046--2066",
    Month="Sep",
    Abstract={Recent evidence points to extra-telomeric, noncanonical roles for telomerase in regulating stem cell function. In this study, human embryonic stem cells (hESCs) were cultured in 20% or 2% O2 microenvironments for up to 5 days and evaluated for telomerase reverse transcriptase (TERT) expression and telomerase activity. Results showed increased cell survival and maintenance of the undifferentiated state with elevated levels of nuclear TERT in 2% O2-cultured hESCs despite no significant difference in telomerase activity compared with their high-O2-cultured counterparts. Pharmacological inhibition of telomerase activity using a synthetic tea catechin resulted in spontaneous hESC differentiation, while telomerase inhibition with a phosphorothioate oligonucleotide telomere mimic did not. Reverse transcription polymerase chain reaction (RT-PCR) analysis revealed variations in transcript levels of full-length and alternate splice variants of TERT in hESCs cultured under varying O2 atmospheres. Steric-blocking of Δα and Δβ hTERT splicing using morpholino oligonucleotides altered the hTERT splicing pattern and rapidly induced spontaneous hESC differentiation that appeared biased toward endomesodermal and neuroectodermal cell fates, respectively. Together, these results suggest that post-transcriptional regulation of TERT under varying O2 microenvironments may help regulate hESC survival, self-renewal, and differentiation capabilities through expression of extra-telomeric telomerase isoforms.},
    Note={[PubMed Central:\href{http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4142780}{PMC4142780}] [DOI:\href{http://dx.doi.org/10.1089/scd.2013.0373}{10.1089/scd.2013.0373}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/24749509}{24749509}] }
    }
  • T. F. Wu, Y. L. Yao, I. L. Lai, T. H. Lee, D. A. Underhill, and W. M. Yang, “PAX3 loads onto pericentromeric heterochromatin during S phase through PARP1,” Anticancer res., vol. 34, iss. 9, pp. 4717-4722, 2014.
    [Bibtex]
    @Article{pmid25202049,
    Author="Wu, T. F. and Yao, Y. L. and Lai, I. L. and Lee, T. H. and Underhill, D. A. and Yang, W. M. ",
    Title="{{P}{A}{X}3 loads onto pericentromeric heterochromatin during {S} phase through {P}{A}{R}{P}1}",
    Journal="Anticancer Res.",
    Year="2014",
    Volume="34",
    Number="9",
    Pages="4717--4722",
    Month="Sep",
    Abstract={Proper re-establishment of heterochromatin after each round of DNA replication is critical to the preservation of cell identity. Paired box 3 (PAX3), a transcription factor important in embryonic development, was found to mediate the formation of pericentromeric heterochromatin. However, how PAX3 recognizes the heterochromatic environment and re-establishes it after DNA replication remains unclear.\\ Cell-cycle synchronization, fluorescence microscopic analyses, and co-immunoprecipitation were used to analyze the heterochromatic localization of PAX3 in HEK 293 cells and NIH 3T3 cells.\\ We found that PAX3 binds pericentromeric heterochromatin during middle-to-late S phase. Loading of PAX3 onto pericentromeric heterochromatin requires poly(ADP-ribose) polymerase 1 (PARP1). Furthermore, loss of PAX3 or PARP1 delays cell-cycle progression through the S phase.\\ Our results reveal how PAX3 recognizes and maintains pericentromeric heterochromatin at the S phase of the cell cycle.},
    Note={[PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/25202049}{25202049}] }
    }
  • [DOI] A. Bilichak, Y. Yao, and I. Kovalchuk, “Transient down-regulation of the RNA silencing machinery increases efficiency of agrobacterium-mediated transformation of arabidopsis,” Plant biotechnology journal, vol. 12, iss. 5, pp. 590-600, 2014.
    [Bibtex]
    @article{bilichak_transient_2014,
    abstract = {Summary: Agrobacterium tumefaciens is a plant pathogen that is widely used in plant transformation. As the process of transgenesis includes the delivery of single-stranded T-{DNA} molecule, we hypothesized that transformation rate may negatively correlate with the efficiency of the {RNA}-silencing machinery. Using mutants compromised in either the transcriptional or post-transcriptional gene-silencing pathways, two inhibitors of stable transformation were revealed-{AGO}2 and {NRPD}1a. Furthermore, an immunoprecipitation experiment has shown that {NRPD}1, a subunit of Pol {IV}, directly interacts with Agrobacterium T-{DNA} in planta. Using the Tobacco rattle virus ({TRV})-based virus-induced gene silencing ({VIGS}) technique, we demonstrated that the transient down-regulation of the expression of either {AGO}2 or {NRPD}1a genes in reproductive organs of Arabidopsis, leads to an increase in transformation rate. We observed a 6.0- and 3.5-fold increase in transformation rate upon transient downregulation of either {AGO}2 or {NRPD}1a genes, respectively. This is the first report demonstrating the increase in the plant transformation rate via {VIGS}-mediated transient down-regulation of the components of epigenetic machinery in reproductive tissue. {\copyright} 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley \& Sons Ltd.},
    author = {Bilichak, A. and Yao, Y. and Kovalchuk, I.},
    citeulike-article-id = {13477198},
    citeulike-linkout-0 = {http://dx.doi.org/10.1111/pbi.12165},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84901603435\&\#38;partnerID=40\&\#38;md5=1373f80f2c4511fa985ef45b7244885b},
    doi = {10.1111/pbi.12165},
    journal = {Plant Biotechnology Journal},
    keywords = {agrobacterium, arabidopsis, nicotiana, rattle, tabacum, thaliana, tobacco, tumefaciens, virus, *file-import-15-01-07},
    note = {cited By 0},
    number = {5},
    pages = {590--600},
    posted-at = {2015-01-07 18:50:46},
    priority = {2},
    title = {Transient down-regulation of the {RNA} silencing machinery increases efficiency of agrobacterium-mediated transformation of arabidopsis},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84901603435\&partnerID=40\&md5=1373f80f2c4511fa985ef45b7244885b},
    volume = {12},
    year = {2014}
    }
  • [DOI] B. Kolb, R. Mychasiuk, and R. Gibb, “Brain development, experience, and behavior,” Pediatric blood and cancer, vol. 61, iss. 10, pp. 1720-1723, 2014.
    [Bibtex]
    @article{kolb_brain_2014,
    abstract = {{Brain development progresses through a series of stages beginning with neurogenesis and progressing to neural migration, maturation, synaptogenesis, pruning, and myelin formation. This review examines the literature on how early experiences alter brain development, including environmental events such as sensory stimuli, early stress, psychoactive drugs, parent-child relationships, peer relationships, intestinal flora, diet, and radiation. This sensitivity of the brain to early experiences has important implications for understanding neurodevelopmental disorders as well as the effect of medical interventions in children. {\copyright} 2013 Wiley Periodicals, Inc.}},
    author = {Kolb, B. and Mychasiuk, R. and Gibb, R.},
    citeulike-article-id = {13477197},
    citeulike-linkout-0 = {http://dx.doi.org/10.1002/pbc.24908},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84908506680\&\#38;partnerID=40\&\#38;md5=59ed4bb953b7365ea6c0ea8ef2a0fbe3},
    doi = {10.1002/pbc.24908},
    journal = {Pediatric Blood and Cancer},
    keywords = {behavior, brain, cerebral, child, development, environment, environmental, epigenetics, humans, neurogenesis, neuronal, plasticity, stimulation, *file-import-15-01-07},
    note = {cited By 1},
    number = {10},
    pages = {1720--1723},
    posted-at = {2015-01-07 18:50:46},
    priority = {2},
    title = {{Brain development, experience, and behavior}},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84908506680\&partnerID=40\&md5=59ed4bb953b7365ea6c0ea8ef2a0fbe3},
    volume = {61},
    year = {2014}
    }
  • Thakur, Singla, Chen, Tran, Yang, Salazar, Magliocco, Klimowicz, Jirik, and Riabowol, “Reduced ING1 levels in breast cancer promotes metastasis,” Oncotarget, vol. 5, iss. 12, pp. 4244-4256, 2014.
    [Bibtex]
    @article{thakur_reduced_2014,
    abstract = {{INhibitor} of Growth 1 ({ING}1) expression is repressed in breast carcinomas, but its role in breast cancer development and metastasis is unknown. {ING}1 levels were quantified in {\\textgreater}500 patient samples using automated quantitative fluorescence immunohistochemistry, and data were analysed for correlations to patient outcome. Effects of altering {ING} levels were examined in microarrays and metastasis assays in vitro, and in a mouse metastasis model in vivo. {ING}1 levels were lower in tumors compared to adjacent normal breast tissue and correlated with tumor size (p=0.019) and distant recurrence (p=0.001) in {ER}- or Her2+ patients. In these patients {ING}1 predicted disease-specific and distant metastasis-free survival. Transcriptome analysis showed that the pathway most affected by {ING}1 was breast cancer (p = 0.0008). Decreasing levels of {ING}1 increased, and increasing levels decreased, migration and invasion of {MDA}-{MB}231 cells in vitro. {ING}1 overexpression also blocked cancer cell metastasis in vivo and eliminated tumor-induced mortality in mouse models. Our data show that {ING}1 protein levels are downregulated in breast cancer and for the first time, we show that altering their levels regulates metastasis in vitro and in vivo, which indicates that {ING}1 may have a therapeutic role for inhibiting metastasis of breast cancer.},
    author = {Thakur and Singla and Chen and Tran and Yang and Salazar and Magliocco and Klimowicz and Jirik and Riabowol},
    citeulike-article-id = {13477196},
    citeulike-linkout-0 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84905113829\&\#38;partnerID=40\&\#38;md5=76003c0525a70dba625815d41714d8df},
    journal = {Oncotarget},
    keywords = {1, 2, analysis, animal, article, assay, association, automated, bioassay, breast, cancer, cell, clinical, control, controlled, disease, distant, down, drug, epidermal, estrogen, experiment, expression, factor, female, fluorescence, free, function, gene, growth, histochemistry, human, immunohistochemistry, in, inhibitor, invasion, major, metastasis, microarray, migration, model, mouse, nonhuman, of, oncoprotein, prediction, prognosis, protein, quantitative, receptor, recurrence, regulation, specific, study, survival, tissue, transcriptome, tumor, unclassified, upregulation, vitro, vivo, volume, *file-import-15-01-07},
    note = {cited By 0},
    number = {12},
    pages = {4244--4256},
    posted-at = {2015-01-07 18:50:46},
    priority = {2},
    title = {Reduced {ING}1 levels in breast cancer promotes metastasis},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84905113829\&partnerID=40\&md5=76003c0525a70dba625815d41714d8df},
    volume = {5},
    year = {2014}
    }
  • [DOI] Bathe and Farshidfar, “From genotype to functional phenotype: Unraveling the metabolomic features of colorectal cancer,” Genes, vol. 5, iss. 3, pp. 536-560, 2014.
    [Bibtex]
    @article{bathe_genotype_2014,
    abstract = {Much effort in recent years has been expended in defining the genomic and epigenetic alterations that characterize colorectal adenocarcinoma and its subtypes. However, little is known about the functional ramifications related to various subtypes. Metabolomics, the study of small molecule intermediates in disease, provides a snapshot of the functional phenotype of colorectal cancer. Data, thus far, have characterized some of the metabolic perturbations that accompany colorectal cancer. However, further studies will be required to identify biologically meaningful metabolic subsets, including those corresponding to specific genetic aberrations. Moreover, further studies are necessary to distinguish changes due to tumor and the host response to tumor. {\copyright} 2014 by the authors; licensee {MDPI}, Basel, Switzerland.},
    author = {Bathe and Farshidfar},
    citeulike-article-id = {13477195},
    citeulike-linkout-0 = {http://dx.doi.org/10.3390/genes5030536},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84905588913\&\#38;partnerID=40\&\#38;md5=fe12f3ee4b2ca37c97134dfd78e8a360},
    doi = {10.3390/genes5030536},
    journal = {Genes},
    keywords = {*file-import-15-01-07},
    note = {cited By 0},
    number = {3},
    pages = {536--560},
    posted-at = {2015-01-07 18:50:46},
    priority = {2},
    title = {{From genotype to functional phenotype: Unraveling the metabolomic features of colorectal cancer}},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84905588913\&partnerID=40\&md5=fe12f3ee4b2ca37c97134dfd78e8a360},
    volume = {5},
    year = {2014}
    }
  • [DOI] M. H. Hudy, S. L. Traves, and D. Proud, “Transcriptional and epigenetic modulation of human rhinovirus-induced CXCL10 production by cigarette smoke,” American journal of respiratory cell and molecular biology, vol. 50, iss. 3, pp. 571-582, 2014.
    [Bibtex]
    @article{hudy_transcriptional_2014,
    abstract = {Human rhinovirus ({HRV}) triggers exacerbations of asthma and chronic obstructive pulmonary disease. Cigarette smoking is the primary risk factor for the development of chronic obstructive pulmonary disease, and 25\% of individuals with asthma smoke. Smokers experience both longer and more severe colds. We previously showed that cigarette smoke extract ({CSE}) inhibited {HRV}-induced expression of a range of epithelial antiviral molecules. Here, we use {CXCL}10 as a model antiviral gene to examine the mechanisms by which {CSE} inhibits epithelial antiviral immunity. {HRV}-induced {CXCL}10 transcription depends on activation of {NF}-κB and {IFN}-regulatory factor-1 ({IRF}-1), and we now also implicate two signal transducer and activator of transcription ({STAT}) consensus sequences in the {CXCL}10 promoter in {HRV}-induced {CXCL}10 expression. {CSE} inhibited {HRV}-induced activation and nuclear translocation/binding of both {NF}-κB, and {IRF}-1 to their respective recognition sequences in the {CXCL}10 promoter.{HRValso} induced formation of complexes at the {STAT} region in the {CXCL}10 promoter, and {HRV}-induced activation of {STAT}-1 was inhibited by {CSE}. In addition, {CSE} inhibited {HRV}-induced chromatin accessibility around the transcriptional start site of the {CXCL}10 promoter. Although {CSE} inhibited {HRV}-induced expression of both the viral double-stranded {RNA} sensors, retinoic acid-inducible gene-I and melanoma differentiation-associated gene ({MDA}) 5, only specific short interfering {RNA} ({siRNA}) to {MDA}5, but not nontargeting {siRNA}, or {siRNA} to retinoic acid-inducible gene-I, inhibited {HRV}-induced {CXCL}10 induction. We conclude that {CSE} reduces chromatin accessibility and inhibits viral signaling via {NF}-κB, {IRF}-1, {STAT}-1, and {MDA}5. Thus, we show that {CSE} can simultaneously modulate multiple pathways linked to innate immune responses to {HRV} infection. Copyright {\copyright} 2014 by the American Thoracic Society.},
    author = {Hudy, M. H. and Traves, S. L. and Proud, D.},
    citeulike-article-id = {13477194},
    citeulike-linkout-0 = {http://dx.doi.org/10.1165/rcmb.2013-0129OC},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84895525011\&\#38;partnerID=40\&\#38;md5=4eab4753047111de3d64ee27aaa2deac},
    doi = {10.1165/rcmb.2013-0129OC},
    journal = {American Journal of Respiratory Cell and Molecular Biology},
    keywords = {1, 10, 2, 3, a16, acid, adhesion, and, article, assay, assembly, b, binding, cell, cells, chain, chemokine, chromatin, cigarette, complex, consensus, controlled, cxcl10, cytokine, dead-box, dehydrogenase, disassembly, double, enhancer, enzyme, epigenesis, epigenetics, epithelial, expression, factor, factor-1, formation, gamma, gel, genetic, genomic, glyceraldehyde, helicases, human, humans, i, immunity, immunoglobulin, immunosorbent, inducible, infection, initiation, innate, intercellular, interfering, interferon, internalization, like, line, linked, lung, mobility, molecule, nf-kappa, nonhuman, phosphate, phosphorylation, polymerase, production, promoter, protein, reaction, real, receptor, region, regions, regulation, regulatory, release, repeat, retinoic, reverse, rhinovirus, rna, sequence, shift, signal, sites, small, smoke, smoking, stat, stat1, stranded, study, tandem, time, toll, transcription, transduction, transfection, transient, ubiquitination, up-regulation, *file-import-15-01-07},
    note = {cited By 1},
    number = {3},
    pages = {571--582},
    posted-at = {2015-01-07 18:50:46},
    priority = {2},
    title = {Transcriptional and epigenetic modulation of human rhinovirus-induced {CXCL}10 production by cigarette smoke},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84895525011\&partnerID=40\&md5=4eab4753047111de3d64ee27aaa2deac},
    volume = {50},
    year = {2014}
    }
  • [DOI] S. Megha, U. Basu, and N. N. V. Kav, “Metabolic engineering of cold tolerance in plants,” Biocatalysis and agricultural biotechnology, vol. 3, iss. 1, pp. 88-95, 2014.
    [Bibtex]
    @article{megha_metabolic_2014,
    abstract = {{Low temperature stress is one of the major abiotic stress challenging the growth and productivity of economically important crops. Both chilling and freezing temperatures have severe effects on growth of plants and have resulted in temperate plants, such as perennial rye grass and wheat to evolve mechanisms to avoid or, at the very least, minimize this damage. Accumulating osmoprotectants including glycine betaine, sugars (trehalose and fructans), polyamines, changes in lipid membrane profile, photosynthetic acclimation along with extensive reprogramming at molecular level help temperate plants acquire tolerance to low temperatures. In this review, we have focused mainly on metabolic engineering of plants by introduction of biosynthetic genes involved in various metabolic pathways. Availability of genomic, transcriptomic sequences combined with post-transcriptional data is beginning to link the gene function, regulatory networks and epigenetic states to different phenotypes. Generation of this knowledge together with our ability to manipulate genes involved in mediating tolerance to various stressors including low temperature will lead to the development of cold-resistant genotypes. {\copyright} 2013 Elsevier Ltd.}},
    author = {Megha, S. and Basu, U. and Kav, N. N. V.},
    citeulike-article-id = {13477193},
    citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.bcab.2013.11.007},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84894231016\&\#38;partnerID=40\&\#38;md5=0cab3ad86a13abbf3315dcb3c6200188},
    doi = {10.1016/j.bcab.2013.11.007},
    journal = {Biocatalysis and Agricultural Biotechnology},
    keywords = {*file-import-15-01-07},
    note = {cited By 0},
    number = {1},
    pages = {88--95},
    posted-at = {2015-01-07 18:50:46},
    priority = {2},
    title = {{Metabolic engineering of cold tolerance in plants}},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84894231016\&partnerID=40\&md5=0cab3ad86a13abbf3315dcb3c6200188},
    volume = {3},
    year = {2014}
    }
  • Bose, Thakur, Brockton, Klimowicz, Kornaga, Nakoneshny, Riabowol, and Dort, “Tumor cell apoptosis mediated by cytoplasmic ING1 is associated with improved survival in oral squamous cell carcinoma patients,” Oncotarget, vol. 5, iss. 10, pp. 3210-3219, 2014.
    [Bibtex]
    @article{bose_tumor_2014,
    abstract = {The {ING}1 epigenetic regulator and tumor suppressor plays a central role in apoptosis. The Ing1 gene is functionally inactivated in many cancer types but is rarely mutated. Although most studies have implicated the major {ING}1 isoform, p33ING1b, in nuclear apoptotic signalling, we recently discovered a novel and potent apoptosis-inducing effect of p33ING1b translocation to the mitochondria in response to {DNA} damage. In the present study, we examined the impact of cytoplasmic/mitochondrial localization of p33ING1b in oral squamous cell carcinoma ({OSCC}) patient samples and explored the therapeutic potential of adenovirally-overexpressed p33ING1b in {OSCC} cell lines in combination with ionizing radiation ({IR}) treatment. In contrast with previous reports, we found that p33ING1b protein and {mRNA} levels are higher in {OSCC} compared to normal epithelial cells. In {OSCC} patient samples, higher levels of intra-tumoral cytoplasmic p33ING1b correlated with increased apoptotic markers and significantly better patient survival. This association was strongest in patients who received post-operative radiotherapy. {IR} treatment induced p33ING1b translocation to the mitochondria and adenoviral-p33ING1b synergized with {IR} to kill {OSCC} cells. Our results identify a novel functional relationship between cytoplasmic p33ING1b and patient survival and highlight the potential for the use of p33ING1b as a therapeutic agent in combination with adjuvant radiotherapy in {OSCC}. {\copyright} 2008-2014 Impact Journals, {LLC}.},
    author = {Bose and Thakur and Brockton and Klimowicz and Kornaga and Nakoneshny and Riabowol and Dort},
    citeulike-article-id = {13477192},
    citeulike-linkout-0 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84902106858\&\#38;partnerID=40\&\#38;md5=c6646ccc76dc09b9fbcc98aeed51622b},
    journal = {Oncotarget},
    keywords = {adjuvant, adult, apoptosis, article, bcl, cancer, carcinoma, cell, clinical, cytoplasm, death, disease, drug, expression, female, human, ionizing, killing, localization, major, male, messenger, mouth, p33ing1b, protein, radiation, rna, specific, squamous, study, suppressor, survival, therapy, tissue, transport, tumor, unclassified, xl, *file-import-15-01-07},
    note = {cited By 0},
    number = {10},
    pages = {3210--3219},
    posted-at = {2015-01-07 18:50:46},
    priority = {2},
    title = {Tumor cell apoptosis mediated by cytoplasmic {ING}1 is associated with improved survival in oral squamous cell carcinoma patients},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84902106858\&partnerID=40\&md5=c6646ccc76dc09b9fbcc98aeed51622b},
    volume = {5},
    year = {2014}
    }
  • [DOI] Schmeling, Horneff, Benseler, and Fritzler, “Pharmacogenetics: can genes determine treatment efficacy and safety in JIA?,” Nature reviews rheumatology, vol. 10, iss. 11, pp. 682-690, 2014.
    [Bibtex]
    @article{schmeling_pharmacogenetics:_2014,
    abstract = {Juvenile idiopathic arthritis ({JIA}) is the most common chronic rheumatic condition in childhood, with many children requiring immunomodulatory therapies for many years following diagnosis. A considerable proportion of children experience therapeutic inefficacy or substantial adverse effects, or both, but a lack of reliable clinical indicators and biomarkers to predict treatment response prevents optimization of existing therapies. The identification of valid candidate gene variants involved in the pathways of methotrexate and etanercept, the most commonly used medications in {JIA}, has seen little success to date. The limited success of these studies is possibly due to the presence of confounding variables in the study populations, the heterogeneity of outcome parameters used to determine treatment response and the small number of candidate gene variants analysed. The first genome-wide pharmacogenetic study in {JIA} has identified gene regions of particular biological interest, but these findings require validation. Moreover, epigenetic mechanisms as well as ontogeny processes might be additional factors influencing drug responses. Access to large, well-documented {JIA} cohorts and the rapid development of advanced genome analytics is ushering in a personalized approach to treatment. The discovery of new pharmacogenomic biomarkers and systems pathways can provide new drug targets and predictive tools for improved drug response and fewer adverse drug reactions in {JIA}.},
    author = {Schmeling and Horneff and Benseler and Fritzler},
    citeulike-article-id = {13477191},
    citeulike-linkout-0 = {http://dx.doi.org/10.1038/nrrheum.2014.140},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84908504811\&\#38;partnerID=40\&\#38;md5=f976e2396d4453bf5b89434e8c752713},
    doi = {10.1038/nrrheum.2014.140},
    journal = {Nature Reviews Rheumatology},
    keywords = {10, 5, abcb1, abcc3, acid, activity, adora2a, allele, amino, arthritis, association, atic, cftr, conductance, cystic, dose, drug, efficacy, enthesitis, enzyme, epigenetics, etanercept, factor, fadh2, fibrosis, gamma, gastrointestinal, gene, genetic, genome, genotype, ggh, glutamyl, human, hydrolase, identification, immunomodulation, interaction, itpa, juvenile, label, low, metabolism, methotrexate, methylenetetrahydrofolate, mthfr, necrosis, nucleotide, off, ontogeny, pharmacogenetics, polymorphism, promoter, protein, psoriatic, reductase, region, regulation, regulator, response, review, rheumatoid, safety, single, stat, substitution, tgif1, toxicity, transmembrane, treatment, tumor, use, variability, zmiz1, *file-import-15-01-07},
    note = {cited By 0},
    number = {11},
    pages = {682--690},
    posted-at = {2015-01-07 18:50:45},
    priority = {2},
    title = {Pharmacogenetics: Can genes determine treatment efficacy and safety in {JIA}?},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84908504811\&partnerID=40\&md5=f976e2396d4453bf5b89434e8c752713},
    volume = {10},
    year = {2014}
    }
  • [DOI] A. Bilichak and I. Kovalchuk, “Manipulation of epigenetic factors and the DNA repair machinery for improving the frequency of plant transformation,” Biocatalysis and agricultural biotechnology, vol. 3, iss. 1, pp. 7-13, 2014.
    [Bibtex]
    @article{bilichak_manipulation_2014,
    abstract = {Plant genetic engineering involves the introduction of foreign {DNA} into the plant genome in order to enhance/modify plant traits. In transgenic plants, it is difficult to achieve stable and predictable transgene expression over subsequent generations. Largely, this is due to the lack of critical understanding of plant perception and response to the artificially introduced foreign {DNA}. Recent reports have revealed components of the epigenetic module that may affect transgene stability at both pre- and post-integration steps. Furthermore, the integration of the transgene has been shown to be strictly dependent on the {DNA} repair machinery. In this review, we briefly summarize genetic and epigenetic factors whose manipulation can enhance the efficiency of plant transformation and the quality of genetically engineered transgenic plants. {\copyright} 2013 Elsevier Ltd.},
    author = {Bilichak, A. and Kovalchuk, I.},
    citeulike-article-id = {13477190},
    citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.bcab.2013.08.006},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84894235742\&\#38;partnerID=40\&\#38;md5=62c36a1b9df57052bc17ea2a354c2090},
    doi = {10.1016/j.bcab.2013.08.006},
    journal = {Biocatalysis and Agricultural Biotechnology},
    keywords = {*file-import-15-01-07},
    note = {cited By 0},
    number = {1},
    pages = {7--13},
    posted-at = {2015-01-07 18:50:45},
    priority = {2},
    title = {Manipulation of epigenetic factors and the {DNA} repair machinery for improving the frequency of plant transformation},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84894235742\&partnerID=40\&md5=62c36a1b9df57052bc17ea2a354c2090},
    volume = {3},
    year = {2014}
    }
  • [DOI] Letourneau, Giesbrecht, Bernier, and Joschko, “How Do Interactions Between Early Caregiving Environment and Genes Influence Health and Behavior?,” Biological research for nursing, vol. 16, iss. 1, pp. 83-94, 2014.
    [Bibtex]
    @article{letourneau_how_2014,
    abstract = {To promote optimal health and behavioral outcomes in children, nurses have long supported parents in providing the best possible care and nurturance to their offspring. A growing body of neuroscience research argues convincingly for the combined influences of genes and early caregiving on producing an individual's unique health and behavioral phenotype. In this article, we systematically review studies that demonstrate the relationship between qualities of early caregiving and genetic propensity to health and behavioral outcomes. From an initial set of 255 articles, 24 articles met our inclusion criteria. The outcomes fall into four distinct groups: hypothalamic-pituitary-adrenal ({HPA}) response to stress, externalizing behavior, internalizing behavior, and disorganized attachment. In the articles, authors examined genes that code for the 5-hydroxy tryptamine (serotonin) transporter genes linked polymorphic region [5-{HTTLPR}] serotonin transporter promoter, D4 dopamine receptor, brain-derived neurotrophic factor, and monoamine oxidase A promoter. The reviewed studies suggest that the effect of the early rearing environment on gene expression relates mainly to {HPA} response to stress, whereas interactions between genes and caregiving mainly relate to behavior and attachment. Findings have implications for nurses focused on advocacy, prevention, and intervention to support the healthy development of children in families faced with adversity. {\copyright} The Author(s) 2012.},
    author = {Letourneau and Giesbrecht and Bernier and Joschko},
    citeulike-article-id = {13477189},
    citeulike-linkout-0 = {http://dx.doi.org/10.1177/1099800412463602},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84890630598\&\#38;partnerID=40\&\#38;md5=35d6297db84e23bef496d0964b29c2d6},
    doi = {10.1177/1099800412463602},
    journal = {Biological Research for Nursing},
    keywords = {article, attachment, behavior, caregiver, caregivers, early, environment, environments, epigenetics, expression, gene, gene-by-environment, gene-environment, genotype, health, human, humans, interaction, interactions, rearing, status, *file-import-15-01-07},
    note = {cited By 0},
    number = {1},
    pages = {83--94},
    posted-at = {2015-01-07 18:50:45},
    priority = {2},
    title = {{How Do Interactions Between Early Caregiving Environment and Genes Influence Health and Behavior?}},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84890630598\&partnerID=40\&md5=35d6297db84e23bef496d0964b29c2d6},
    volume = {16},
    year = {2014}
    }
  • C. Sidler, R. Woycicki, D. Li, B. Wang, I. Kovalchuk, and O. Kovalchuk, “A role for SUV39h1-mediated h3k9 trimethylation in the control of genome stability and senescence in WI38 human diploid lung fibroblasts,” Aging, vol. 6, iss. 7, pp. 545-563, 2014.
    [Bibtex]
    @article{sidler_role_2014,
    abstract = {Cellular senescence has been associated with the age-dependent decline in tissue repair and regeneration, the increasing deterioration of the immune system, and the age-dependent increase in the incidence of cancer. Here, we show that senescence of human lung fibroblast {WI}-38 cells is associated with extensive changes to the gene expression profile, including the differential expression of transcriptional and epigenetic regulators. Among those, {SUV}39H1 was downregulated in senescent cells, correlated with a decrease in global H3K9 trimethylation, reduced H3K9me3 levels in repetitive {DNA} sequence regions such as satellites and transposable elements, and increased transcription of these repetitive {DNA} sequences. This indicates that {SUV}39H1 plays a role in limiting genomic instability in dividing cells and suggests that {SUV}39H1 downregulation may contribute to the establishment of senescence by increasing genomic instability. Additionally, the manipulation of {SUV}39H1 expression levels resulted in altered cell cycle distribution, suggesting a causal role of {SUV}39H1 in the establishment of cellular senescence. Thus, based on our findings and the results from previous reports, we propose a model in which {SUV}39H1 downregulation promotes the establishment of cellular senescence. {\copyright} Sidler et al.},
    author = {Sidler, C. and Woycicki, R. and Li, D. and Wang, B. and Kovalchuk, I. and Kovalchuk, O.},
    citeulike-article-id = {13477188},
    citeulike-linkout-0 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84905716689\&\#38;partnerID=40\&\#38;md5=811339e238f67718580afe15fe660d68},
    journal = {Aging},
    keywords = {*file-import-15-01-07},
    note = {cited By 1},
    number = {7},
    pages = {545--563},
    posted-at = {2015-01-07 18:50:45},
    priority = {2},
    title = {A role for {SUV}39H1-mediated H3K9 trimethylation in the control of genome stability and senescence in {WI}38 human diploid lung fibroblasts},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84905716689\&partnerID=40\&md5=811339e238f67718580afe15fe660d68},
    volume = {6},
    year = {2014}
    }
  • [DOI] Z. Migicovsky, Y. Yao, and I. Kovalchuk, “Transgenerational phenotypic and epigenetic changes in response to heat stress in Arabidopsis thaliana,” Plant signaling and behavior, vol. 9, iss. {FEB}, 2014.
    [Bibtex]
    @article{migicovsky_transgenerational_2014,
    abstract = {Exposure to heat stress causes physiological and epigenetic changes in plants, which may also be altered in the progeny. We compared the progeny of stressed and control Arabidopsis thaliana wild type and Dicer-like mutant dcl2, dcl3, and dcl4 plants for variations in physiology and molecular profile, including global genome methylation, {mRNA} levels, and histone modifications in the subset of differentially expressed genes at normal conditions and in response to heat stress. We found that the immediate progeny of heat-stressed plants had fewer, but larger leaves, and tended to bolt earlier. Transposon expression was elevated in the progeny of heat-stressed plants, and heat stress in the same generation tended to decrease global genome methylation. Progeny of stressed plants had increased expression of {HSFA}2, and reduction in {MSH}2, {ROS}1, and several {SUVH} genes. Gene expression positively correlated with permissive histone marks and negatively correlated with repressive marks. Overall, the progeny of heat stressed plants varied in both their physiology and epigenome and dcl2 and dcl3 mutants were partially deficient for these changes. {\copyright} 2014 Landes Bioscience.},
    author = {Migicovsky, Z. and Yao, Y. and Kovalchuk, I.},
    citeulike-article-id = {13477187},
    citeulike-linkout-0 = {http://dx.doi.org/10.4161/psb.27971},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84899142501\&\#38;partnerID=40\&\#38;md5=9a4155f1cd1c5be5757ff3e83ab8ef80},
    doi = {10.4161/psb.27971},
    journal = {Plant Signaling and Behavior},
    keywords = {*file-import-15-01-07},
    note = {cited By 0},
    number = {{FEB}},
    posted-at = {2015-01-07 18:50:45},
    priority = {2},
    title = {{Transgenerational phenotypic and epigenetic changes in response to heat stress in Arabidopsis thaliana}},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84899142501\&partnerID=40\&md5=9a4155f1cd1c5be5757ff3e83ab8ef80},
    volume = {9},
    year = {2014}
    }
  • [DOI] Leach, Prefontaine, Hurd, and Crespi, “The imprinted gene LRRTM1 mediates schizotypy and handedness in a nonclinical population,” Journal of human genetics, vol. 59, iss. 6, pp. 332-336, 2014.
    [Bibtex]
    @article{leach_imprinted_2014,
    abstract = {Imprinted genes have been posited to have important roles in human brain development and cognition, but their effects in nonclinical populations have yet to be investigated. Single-nucleotide polymorphisms ({SNPs}) of the imprinted gene {LRRTM}1 have previously been associated with schizophrenia risk and with handedness in individuals with dyslexia. We tested the hypothesis that genetic variation ({SNPs}) and epigenetic variation (methylation) in this gene are associated with schizotypy and handedness in a nonclinical population. Risk alleles of the three schizophrenia-linked {SNPs} were associated with significantly and substantially higher levels of total schizotypy. Variation in {SNP} genotypes was not associated with handedness, but levels of methylation in a block of {CpG} sites in the putative {LRRTM}1 promoter region were associated with more-mixed handedness. These findings provide evidence of continuity between schizophrenia and schizotypy with regard to the psychological effects of allelic variation in this imprinted gene, and show that epigenetic variation in an imprinted gene mediates the development and expression of human handedness. {\copyright} 2014 The Japan Society of Human Genetics. All rights reserved.},
    author = {Leach and Prefontaine and Hurd and Crespi},
    citeulike-article-id = {13477186},
    citeulike-linkout-0 = {http://dx.doi.org/10.1038/jhg.2014.30},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84903182713\&\#38;partnerID=40\&\#38;md5=ee1201bec98b018c2389bec11b541292},
    doi = {10.1038/jhg.2014.30},
    journal = {Journal of Human Genetics},
    keywords = {allele, article, association, clinical, cpg, disequilibrium, dna, drug, epigenetics, female, gene, genetic, genome, genotype, handedness, haplotype, human, imprinting, island, left, linkage, lrrtm1, major, male, membrane, methylation, modification, nucleotide, polymorphism, promoter, protein, pyrosequencing, region, right, risk, schizophrenia, single, study, unclassified, variability, *file-import-15-01-07},
    note = {cited By 2},
    number = {6},
    pages = {332--336},
    posted-at = {2015-01-07 18:50:45},
    priority = {2},
    title = {The imprinted gene {LRRTM}1 mediates schizotypy and handedness in a nonclinical population},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84903182713\&partnerID=40\&md5=ee1201bec98b018c2389bec11b541292},
    volume = {59},
    year = {2014}
    }
  • [DOI] C. Sidler, D. Li, B. Wang, I. Kovalchuk, and O. Kovalchuk, “SUV39h1 downregulation induces deheterochromatinization of satellite regions and senescence after exposure to ionizing radiation,” Frontiers in genetics, vol. 5, iss. {NOV}, 2014.
    [Bibtex]
    @article{sidler_suv39h1_2014,
    abstract = {While the majority of cancer patients are exposed to ionizing radiation during diagnostic and therapeutic procedures, age-dependent differences in radiation sensitivity are not yet well understood. Radiation sensitivity is characterized by the appearance of side effects to radiation therapy, such as secondary malignancies, developmental deficits, and compromised immune function. However, the knowledge of the molecular mechanisms that trigger these side effects is incomplete. Here we used an in vitro system and showed that low-senescent normal human diploid fibroblasts ({WI}-38) senesce in response to 5 Gy {IR}, while highly senescent cultures do not show changes in cell cycle regulation and only a slight increase in the percentage of senescent cells. Our study shows that this is associated with changes in the expression of genes responsible for cell cycle progression, apoptosis, {DNA} repair, and aging, as well as transcriptional and epigenetic regulators. Furthermore, we propose a role of the downregulation of {SUV}39H1 expression, a histone methyltransferase that specifically trimethylates H3K9, and the corresponding reduction in H3K9me3 levels in the establishment of {IR}-induced senescence.},
    author = {Sidler, C. and Li, D. and Wang, B. and Kovalchuk, I. and Kovalchuk, O.},
    citeulike-article-id = {13477185},
    citeulike-linkout-0 = {http://dx.doi.org/10.3389/fgene.2014.00411},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84917677984\&\#38;partnerID=40\&\#38;md5=400068bfacf5839ab27b430e044debbc},
    doi = {10.3389/fgene.2014.00411},
    journal = {Frontiers in Genetics},
    keywords = {1, 2, 3, activated, aging, antibody, apoptosis, article, beta, blotting, cell, chain, checkpoint, chromatin, collagen, complementary, connective, controlled, cpg, cycle, cytometry, damage, dehydrogenase, diploidy, dna, dose, down, epigenetics, expression, factor, fibroblast, flow, fluorescein, g, g1, g2, galactosidase, gene, genomic, glyceraldehyde, growth, h3, heterochromatin, histone, human, immunoglobulin, immunoprecipitation, inhibitor, initiation, instability, ionizing, irradiation, island, isothiocyanate, kinase, lung, lysine, metalloproteinase, methylation, methyltransferase, of, overexpression, p21, p53, phase, phosphate, polymerase, profiling, progression, proliferation, protein, radiation, reaction, real, regulation, repair, satellite, senescence, study, suv39h1, time, tissue, transcription, type, upregulation, western, x, *file-import-15-01-07},
    note = {cited By 0},
    number = {{NOV}},
    posted-at = {2015-01-07 18:50:45},
    priority = {2},
    title = {{SUV}39H1 downregulation induces deheterochromatinization of satellite regions and senescence after exposure to ionizing radiation},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84917677984\&partnerID=40\&md5=400068bfacf5839ab27b430e044debbc},
    volume = {5},
    year = {2014}
    }
  • [DOI] Ostrom, Bauchet, Davis, Deltour, Fisher, Langer, Pekmezci, Schwartzbaum, Turner, Walsh, Wrensch, and Barnholtz-Sloan, “The epidemiology of glioma in adults: A state of the science review,” Neuro-oncology, vol. 16, iss. 7, pp. 896-913, 2014.
    [Bibtex]
    @article{ostrom_epidemiology_2014,
    abstract = {Gliomas are the most common primary intracranial tumor, representing 81\% of malignant brain tumors. Although relatively rare, they cause significant mortality and morbidity. Glioblastoma, the most common glioma histology (∼45\% of all gliomas), has a 5-year relative survival of ∼5\%. A small portion of these tumors are caused by Mendelian disorders, including neurofibromatosis, tuberous sclerosis, and Li-Fraumeni syndrome. Genomic analyses of glioma have also produced new evidence about risk and prognosis. Recently discovered biomarkers that indicate improved survival include O 6-methylguanine-{DNA} methyltransferase methylation, isocitrate dehydrogenase mutation, and a glioma cytosine-phosphate-guanine island methylator phenotype. Genome-wide association studies have identified heritable risk alleles within 7 genes that are associated with increased risk of glioma. Many risk factors have been examined as potential contributors to glioma risk. Most significantly, these include an increase in risk by exposure to ionizing radiation and a decrease in risk by history of allergies or atopic disease(s). The potential influence of occupational exposures and cellular phones has also been examined, with inconclusive results. We provide a state of the science review of current research into causes and risk factors for gliomas in adults. {\copyright} 2014 The Author(s).},
    author = {Ostrom and Bauchet and Davis and Deltour and Fisher and Langer and Pekmezci and Schwartzbaum and Turner and Walsh and Wrensch and Barnholtz-Sloan},
    citeulike-article-id = {13477184},
    citeulike-linkout-0 = {http://dx.doi.org/10.1093/neuonc/nou087},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84902489371\&\#38;partnerID=40\&\#38;md5=c14ccc09b06ed48d6ea5da27c7415549},
    doi = {10.1093/neuonc/nou087},
    journal = {Neuro-Oncology},
    keywords = {1, 2, 2a, 2b, adult, allergy, analysis, association, astrocytoma, atopy, cancer, ccdc26, cyclin, cysteine, cytosine, dehydrogenase, dependent, dna, ependymoma, epidemiology, epidermal, exposure, factor, familial, field, frequency, gene, genetic, genome, glioblastoma, glioma, growth, guanine, history, human, incidence, inhibitor, ionizing, isocitrate, kinase, magnetic, medical, meta, methylated, methylation, methyltransferase, mismatch, mlh1, mobile, molecular, mortality, msh2, msh6, mutation, nerve, neurofibromatosis, occupational, oligodendroglioma, oncogene, optic, overall, p53, pathology, pesticide, phenotype, phldb1, phone, phosphate, pilocytic, pms2, prognosis, protein, radiation, rate, receptor, repair, reverse, review, risk, sclerosis, solvent, suppressor, survival, telomerase, time, topic, transcriptase, tuberin, tuberous, tumor, *file-import-15-01-07},
    note = {cited By 5},
    number = {7},
    pages = {896--913},
    posted-at = {2015-01-07 18:50:45},
    priority = {2},
    title = {{The epidemiology of glioma in adults: A state of the science review}},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84902489371\&partnerID=40\&md5=c14ccc09b06ed48d6ea5da27c7415549},
    volume = {16},
    year = {2014}
    }
  • [DOI] R. P. da Silva, K. B. Kelly, A. Al Rajabi, and R. L. Jacobs, “Novel insights on interactions between folate and lipid metabolism,” BioFactors, vol. 40, iss. 3, pp. 277-283, 2014.
    [Bibtex]
    @article{da_silva_novel_2014,
    abstract = {Folate is an essential B vitamin required for the maintenance of {AdoMet}-dependent methylation. The liver is responsible for many methylation reactions that are used for post-translational modification of proteins, methylation of {DNA}, and the synthesis of hormones, creatine, carnitine, and phosphatidylcholine. Conditions where methylation capacity is compromised, including folate deficiency, are associated with impaired phosphatidylcholine synthesis resulting in non-alcoholic fatty liver disease and steatohepatitis. In addition, folate intake and folate status have been associated with changes in the expression of genes involved in lipid metabolism, obesity, and metabolic syndrome. In this review, we provide insight on the relationship between folate and lipid metabolism, and an outlook for the future of lipid-related folate research. {\copyright} 2013 The Authors {BioFactors} published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology.},
    author = {da Silva, R. P. and Kelly, K. B. and Al Rajabi, A. and Jacobs, R. L.},
    citeulike-article-id = {13477183},
    citeulike-linkout-0 = {http://dx.doi.org/10.1002/biof.1154},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84902544544\&\#38;partnerID=40\&\#38;md5=2ea6a35a1bf0435b94cb8ae8c4e2f8bf},
    doi = {10.1002/biof.1154},
    journal = {{BioFactors}},
    keywords = {acid, atherosclerosis, carbon, carnitine, creatine, deficiency, dna, epigenetics, folate, folic, hormone, human, journal, level, lipid, liver, metabolism, methylation, modification, nonhuman, obesity, phosphatidylcholine, priority, protein, review, synthesis, *file-import-15-01-07},
    note = {cited By 0},
    number = {3},
    pages = {277--283},
    posted-at = {2015-01-07 18:50:44},
    priority = {2},
    title = {{Novel insights on interactions between folate and lipid metabolism}},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84902544544\&partnerID=40\&md5=2ea6a35a1bf0435b94cb8ae8c4e2f8bf},
    volume = {40},
    year = {2014}
    }
  • [DOI] Chesnelong, Chaumeil, Blough, Al-Najjar, Stechishin, Chan, Pieper, Ronen, Weiss, Luchman, and Cairncross, “Lactate dehydrogenase a silencing in IDH mutant gliomas,” Neuro-oncology, vol. 16, iss. 5, pp. 686-695, 2014.
    [Bibtex]
    @article{chesnelong_lactate_2014,
    abstract = {{BackgroundMutations} of the isocitrate dehydrogenase 1 and 2 gene ({IDH}1/2) were initially thought to enhance cancer cell survival and proliferation by promoting the Warburg effect. However, recent experimental data have shown that production of 2-hydroxyglutarate by {IDH} mutant cells promotes hypoxia-inducible factor ({HIF})1α degradation and, by doing so, may have unexpected metabolic effects.{MethodsWe} used human glioma tissues and derived brain tumor stem cells ({BTSCs}) to study the expression of {HIF}1α target genes in {IDH} mutant ( mt) and {IDH} wild-type (wt) tumors. Focusing thereafter on the major glycolytic enzyme, lactate dehydrogenase A ({LDHA}), we used standard molecular methods and pyrosequencing-based {DNA} methylation analysis to identify mechanisms by which {LDHA} expression was regulated in human gliomas.{ResultsWe} found that {HIF}1α-responsive genes, including many essential for glycolysis ({SLC}2A1, {PDK}1, {LDHA}, {SLC}16A3), were underexpressed in {IDHmt} gliomas and/or derived {BTSCs}. We then demonstrated that {LDHA} was silenced in {IDH} mt derived {BTSCs}, including those that did not retain the mutant {IDH}1 allele ({mIDHwt}), matched {BTSC} xenografts, and parental glioma tissues. Silencing of {LDHA} was associated with increased methylation of the {LDHA} promoter, as was ectopic expression of mutant {IDH}1 in immortalized human astrocytes. Furthermore, in a search of The Cancer Genome Atlas, we found low expression and high methylation of {LDHA} in {IDHmt} glioblastomas. {ConclusionTo} our knowledge, this is the first demonstration of downregulation of {LDHA} in cancer. Although unexpected findings, silencing of {LDHA} and downregulation of several other glycolysis essential genes raise the intriguing possibility that {IDHmt} gliomas have limited glycolytic capacity, which may contribute to their slow growth and better prognosis. {\copyright} 2013 {\copyright} The Author(s) 2013. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: [email protected]},
    author = {Chesnelong and Chaumeil and Blough and Al-Najjar and Stechishin and Chan and Pieper and Ronen and Weiss and Luchman and Cairncross},
    citeulike-article-id = {13477182},
    citeulike-linkout-0 = {http://dx.doi.org/10.1093/neuonc/not243},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84899415660\&\#38;partnerID=40\&\#38;md5=2260e382adb0b5d8885f71b926c97ca8},
    doi = {10.1093/neuonc/not243},
    journal = {Neuro-Oncology},
    keywords = {1, 1alpha, 5, article, astrocyte, brain, cancer, cell, controlled, dehydrogenase, dependent, dna, drug, enzyme, expression, factor, frequency, gene, glioblastoma, glycolysis, human, hypoxia, immortalization, inducible, isocitrate, isoenzyme, kinase, lactate, mechanism, methylation, mutation, phosphoinositide, promoter, protein, pyrosequencing, region, silencing, stem, study, targeting, tissue, tumor, type, unclassified, wild, xenograft, *file-import-15-01-07},
    note = {cited By 6},
    number = {5},
    pages = {686--695},
    posted-at = {2015-01-07 18:50:44},
    priority = {2},
    title = {Lactate dehydrogenase A silencing in {IDH} mutant gliomas},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84899415660\&partnerID=40\&md5=2260e382adb0b5d8885f71b926c97ca8},
    volume = {16},
    year = {2014}
    }
  • C. Sidler, R. Woycicki, I. Kovalchuk, and O. Kovalchuk, “WI-38 senescence is associated with global and site-specific hypomethylation,” Aging, vol. 6, iss. 7, pp. 564-574, 2014.
    [Bibtex]
    @article{sidler_wi-38_2014,
    abstract = {Cellular senescence plays an important role in the age-dependent functional decline of organs and organ systems, as well as in age-related pathologies, such as cancer. Therefore, a better understanding of its underlying molecular mechanisms is crucial in the search for intervening measures. In this study, we considered the role of {DNA} methylation in senescence. We found that senescence is associated with global {DNA} hypomethylation, but also involves site-specific {DNA} hypo- and hypermethylation. In some cases, this differential methylation may affect gene expression and thereby modulate functional processes within cells. However, the majority of the {CpG} sites that were differentially methylated did not correspond with altered gene expression, suggesting that {DNA} methylation affects senescence by other means also, such as, for instance, genome stability. {\copyright} Sidler et al.},
    author = {Sidler, C. and Woycicki, R. and Kovalchuk, I. and Kovalchuk, O.},
    citeulike-article-id = {13477181},
    citeulike-linkout-0 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84905689935\&\#38;partnerID=40\&\#38;md5=55f38aad0ac53ab5f530ff80340ef374},
    journal = {Aging},
    keywords = {*file-import-15-01-07},
    note = {cited By 0},
    number = {7},
    pages = {564--574},
    posted-at = {2015-01-07 18:50:44},
    priority = {2},
    title = {{WI}-38 senescence is associated with global and site-specific hypomethylation},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84905689935\&partnerID=40\&md5=55f38aad0ac53ab5f530ff80340ef374},
    volume = {6},
    year = {2014}
    }
  • [DOI] Tsai, Chan, Gibeault, Conn, Dheekollu, Domsic, Marmorstein, Schang, and Lieberman, “Viral reprogramming of the Daxx histone h3.3 chaperone during early Epstein-Barr virus infection,” Journal of virology, vol. 88, iss. 24, pp. 14350-14363, 2014.
    [Bibtex]
    @article{tsai_viral_2014,
    abstract = {Host chromatin assembly can function as a barrier to viral infection. Epstein-Barr virus ({EBV}) establishes latent infection as chromatin-assembled episomes in which all but a few viral genes are transcriptionally silent. The factors that control chromatin assembly and guide transcription regulation during the establishment of latency are not well understood. Here, we demonstrate that the {EBV} tegument protein {BNRF}1 binds the histone H3.3 chaperone Daxx to modulate histone mobility and chromatin assembly on the {EBV} genome during the early stages of primary infection. We demonstrate that {BNRF}1 substitutes for the repressive cochaperone {ATRX} to form a ternary complex of {BNRF}1-Daxx-H3.3-H4, using coimmunoprecipitation and size-exclusion chromatography with highly purified components. {FRAP} (fluorescence recovery after photobleaching) assays were used to demonstrate that {BNRF}1 promotes global mobilization of cellular histone H3.3. Mutation of putative nucleotide binding motifs on {BNRF}1 attenuates the displacement of {ATRX} from Daxx. We also show by immunofluorescence combined with fluorescence in situ hybridization that {BNRF}1 is important for the dissociation of {ATRX} and Daxx from nuclear bodies during de novo infection of primary B lymphocytes. Virion-delivered {BNRF}1 suppresses Daxx-{ATRX}-mediated H3.3 loading on viral chromatin as measured by chromatin immunoprecipitation assays and enhances viral gene expression during early infection. We propose that {EBV} tegument protein {BNRF}1 replaces {ATRX} to reprogram Daxx-mediated H3.3 loading, in turn generating chromatin suitable for latent gene expression.},
    author = {Tsai and Chan and Gibeault and Conn and Dheekollu and Domsic and Marmorstein and Schang and Lieberman},
    citeulike-article-id = {13477180},
    citeulike-linkout-0 = {http://dx.doi.org/10.1128/JVI.01895-14},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84911468583\&\#38;partnerID=40\&\#38;md5=1cfc826db7e7ec787895adde4ac7d9b7},
    doi = {10.1128/JVI.01895-14},
    journal = {Journal of Virology},
    keywords = {4, adult, after, and, antiviral, article, assembly, atrx, barr, binding, bnrf1, cell, chromatin, chromatography, coimmunoprecipitation, controlled, course, daxx, disassembly, disease, domain, drug, epstein, expression, fluorescence, function, functions, gel, gene, h3, h33, h4, herpesvirus, histone, human, infection, inhibition, interaction, kinetics, latent, modification, nonhuman, permeation, phenomena, photobleaching, primary, protein, recovery, reprogramming, resistance, study, transport, type, unclassified, viral, virus, wild, *file-import-15-01-07},
    note = {cited By 0},
    number = {24},
    pages = {14350--14363},
    posted-at = {2015-01-07 18:50:43},
    priority = {2},
    title = {{Viral reprogramming of the Daxx histone h3.3 chaperone during early Epstein-Barr virus infection}},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84911468583\&partnerID=40\&md5=1cfc826db7e7ec787895adde4ac7d9b7},
    volume = {88},
    year = {2014}
    }
  • Ashbury, Taylor, Tse, Pang, Louw, Vanner, and King, “Biomarkers measured in buccal and blood leukocyte DNA as proxies for colon tissue global methylation,” International journal of molecular epidemiology and genetics, vol. 5, iss. 2, pp. 120-124, 2014.
    [Bibtex]
    @article{ashbury_biomarkers_2014,
    abstract = {There is increasing interest in clarifying the role of global {DNA} methylation levels in colorectal cancer ({CRC}) etiology. Most commonly, in epidemiologic studies, methylation is measured in {DNA} derived from blood leukocytes as a proxy measure of methylation changes in colon tissue. However, little is known about the correlations between global methylation levels in {DNA} derived from colon tissue and more accessible tissues such as blood or buccal cells. This cross-sectional study utilized {DNA} samples from a screening colonoscopy population to determine to what extent {LINE}-1 methylation levels (as a proxy for genome-wide methylation) in non-target tissue (e.g., blood, buccal cells) refected methylation patterns of colon mucosal tissue directly at risk of developing {CRC}. The strongest Pearson correlation was observed between {LINE}-1 methylation levels in buccal and blood leukocyte {DNA} (r = 0.50; N = 67), with weaker correlations for comparisons between blood and colon tissue (r = 0.36; N = 280), and buccal and colon tissue (r = 0.27; N = 72). These findings of weak/moderate correlations have important implications for interpreting and planning future investigations of epigenetic markers and {CRC} risk.},
    author = {Ashbury and Taylor and Tse and Pang and Louw and Vanner and King},
    citeulike-article-id = {13477179},
    citeulike-linkout-0 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84901749446\&\#38;partnerID=40\&\#38;md5=89fe035e0fcf33b2fefee487f477140f},
    journal = {International Journal of Molecular Epidemiology and Genetics},
    keywords = {1, adenoma, adult, aged, analysis, article, biological, blood, cancer, chain, cheek, clinical, colon, colonoscopy, colorectal, controlled, cpg, cross-sectional, dna, element, expression, female, gene, high, human, interspersed, island, leukocyte, long, major, male, marker, melting, methylation, occult, polymerase, questionnaire, reaction, real, resolution, risk, study, time, tissue, *file-import-15-01-07},
    note = {cited By 2},
    number = {2},
    pages = {120--124},
    posted-at = {2015-01-07 18:50:43},
    priority = {2},
    title = {Biomarkers measured in buccal and blood leukocyte {DNA} as proxies for colon tissue global methylation},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84901749446\&partnerID=40\&md5=89fe035e0fcf33b2fefee487f477140f},
    volume = {5},
    year = {2014}
    }
  • [DOI] Young, Hu, Lainoff, Smith, Diaz, Tucker, Trainor, Schneider, Hallgrímsson, and Marcucio, “Embryonic bauplans and the developmental origins of facial diversity and constraint,” Development (cambridge), vol. 141, iss. 5, pp. 1059-1063, 2014.
    [Bibtex]
    @article{young_embryonic_2014,
    abstract = {{A central issue in biology concerns the presence, timing and nature of phylotypic periods of development, but whether, when and why species exhibit conserved morphologies remains unresolved. Here, we construct a developmental morphospace to show that amniote faces share a period of reduced shape variance and convergent growth trajectories from prominence formation through fusion, after which phenotypic diversity sharply increases. We predict in silico the phenotypic outcomes of unoccupied morphospaces and experimentally validate in vivo that observed convergence is not due to developmental limits on variation but instead from selection against novel trajectories that result in maladaptive facial clefts. These results illustrate how epigenetic factors such as organismal geometry and shape impact facial morphogenesis and alter the locus of adaptive selection to variation in later developmental events. {\copyright} 2014. Published by The Company of Biologists Ltd.}},
    author = {Young and Hu and Lainoff and Smith and Diaz and Tucker and Trainor and Schneider and Hallgr\'{\i}msson and Marcucio},
    citeulike-article-id = {13477178},
    citeulike-linkout-0 = {http://dx.doi.org/10.1242/dev.099994},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84894045302\&\#38;partnerID=40\&\#38;md5=fdec4fd0cbc7629a38aa407c1c9edc6c},
    doi = {10.1242/dev.099994},
    journal = {Development (Cambridge)},
    keywords = {alligators, analysis, and, animals, birds, cleft, crest, cricetinae, crocodiles, evolvability, humans, lip, lizards, mice, multivariate, neural, rats, snakes, turtles, *file-import-15-01-07},
    note = {cited By 3},
    number = {5},
    pages = {1059--1063},
    posted-at = {2015-01-07 18:50:42},
    priority = {2},
    title = {{Embryonic bauplans and the developmental origins of facial diversity and constraint}},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84894045302\&partnerID=40\&md5=fdec4fd0cbc7629a38aa407c1c9edc6c},
    volume = {141},
    year = {2014}
    }
  • [DOI] B. Kolb and A. Muhammad, “Harnessing the power of neuroplasticity for intervention,” Frontiers in human neuroscience, vol. 8, iss. {JUNE}, 2014.
    [Bibtex]
    @article{kolb_harnessing_2014,
    abstract = {{A fundamental property of the brain is its capacity to change with a wide variety of experiences, including injury. Although there are spontaneous reparative changes following injury, these changes are rarely sufficient to support significant functional recovery. Research on the basic principles of brain plasticity is leading to new approaches to treating the injured brain. We review factors that affect synaptic organization in the normal brain, evidence of spontaneous neuroplasticity after injury, and the evidence that factors including postinjury experience, pharmacotherapy, and cell-based therapies, can form the basis of rehabilitation strategies after brain injuries early in life and in adulthood. {\copyright} 2014 Kolb and Muhammad.}},
    author = {Kolb, B. and Muhammad, A.},
    citeulike-article-id = {13477176},
    citeulike-linkout-0 = {http://dx.doi.org/10.3389/fnhum.2014.00377},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84903470105\&\#38;partnerID=40\&\#38;md5=c9c548a45ee944b5a31a7384547b76c2},
    doi = {10.3389/fnhum.2014.00377},
    journal = {Frontiers in Human Neuroscience},
    keywords = {2, a, accident, accumbens, acetylation, activity, age, amphetamine, assessment, brain, ca1, cardiovascular, cell, central, cerebrovascular, coefficient, correlation, cortex, depth, disease, dystonia, electrophysiology, epidermal, epigenetics, erythropoietin, excitability, experience, expression, factor, fibroblast, function, functional, gene, growth, harnessing, hippocampal, indication, injury, inosine, interaction, kidney, learning, lifespan, memory, methylation, microrna, motivation, motor, nerve, nervous, network, neural, neurorehabilitation, neuroscience, nicotine, nogo, nonhuman, nucleus, outcome, performance, period, plasticity, prefrontal, prenatal, presynaptic, proliferation, protein, region, rehabilitation, review, social, stem, stimulation, structure, system, task, therapy, time, treatment, *file-import-15-01-07},
    note = {cited By 0},
    number = {{JUNE}},
    posted-at = {2015-01-07 18:50:42},
    priority = {2},
    title = {{Harnessing the power of neuroplasticity for intervention}},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84903470105\&partnerID=40\&md5=c9c548a45ee944b5a31a7384547b76c2},
    volume = {8},
    year = {2014}
    }
  • [DOI] Sutendra, Kinnaird, Dromparis, Paulin, Stenson, Haromy, Hashimoto, Zhang, Flaim, and Michelakis, “A nuclear pyruvate dehydrogenase complex is important for the generation of acetyl-CoA and histone acetylation,” Cell, vol. 158, iss. 1, pp. 84-97, 2014.
    [Bibtex]
    @article{sutendra_nuclear_2014,
    abstract = {{DNA} transcription, replication, and repair are regulated by histone acetylation, a process that requires the generation of acetyl-coenzyme A ({CoA}). Here, we show that all the subunits of the mitochondrial pyruvate dehydrogenase complex ({PDC}) are also present and functional in the nucleus of mammalian cells. We found that knockdown of nuclear {PDC} in isolated functional nuclei decreased the de novo synthesis of acetyl-{CoA} and acetylation of core histones. Nuclear {PDC} levels increased in a cell-cycle-dependent manner and in response to serum, epidermal growth factor, or mitochondrial stress; this was accompanied by a corresponding decrease in mitochondrial {PDC} levels, suggesting a translocation from the mitochondria to the nucleus. Inhibition of nuclear {PDC} decreased acetylation of specific lysine residues on histones important for G1-S phase progression and expression of S phase markers. Dynamic translocation of mitochondrial {PDC} to the nucleus provides a pathway for nuclear acetyl-{CoA} synthesis required for histone acetylation and epigenetic regulation. {\copyright} 2014 Elsevier Inc.},
    author = {Sutendra and Kinnaird and Dromparis and Paulin and Stenson and Haromy and Hashimoto and Zhang and Flaim and Michelakis},
    citeulike-article-id = {13477175},
    citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.cell.2014.04.046},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84903954689\&\#38;partnerID=40\&\#38;md5=ca013ee103b6d9d17c13739312334b49},
    doi = {10.1016/j.cell.2014.04.046},
    journal = {Cell},
    keywords = {a, acetyl, acetylation, article, cell, checkpoint, coenzyme, complex, controlled, cycle, dehydrogenase, enzyme, epidermal, epigenesis, expression, factor, formation, g1, gene, genetic, growth, histone, histones, human, humans, journal, line, lysine, mammal, mitochondria, nucleus, phase, priority, progression, protein, pyruvate, regulation, s, stress, study, synthesis, transport, tumor, *file-import-15-01-07},
    note = {cited By 10},
    number = {1},
    pages = {84--97},
    posted-at = {2015-01-07 18:50:41},
    priority = {2},
    title = {A nuclear pyruvate dehydrogenase complex is important for the generation of Acetyl-{CoA} and histone acetylation},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84903954689\&partnerID=40\&md5=ca013ee103b6d9d17c13739312334b49},
    volume = {158},
    year = {2014}
    }
  • [DOI] King, Ashbury, Taylor, Tse, Pang, Louw, and Vanner, “A cross-sectional study of global DNA methylation and risk of colorectal adenoma,” BMC cancer, vol. 14, iss. 1, 2014.
    [Bibtex]
    @article{king_cross-sectional_2014,
    abstract = {Background: The methylation of {DNA} is recognized as a key epigenetic mechanism and evidence for its role in the development of several malignancies is accumulating. We evaluated the relationship between global methylation in {DNA} derived from normal appearing colon mucosal tissue and blood leukocytes, and colorectal adenoma risk.Methods: Patients, aged 40 to 65, scheduled for a screening colonoscopy were recruited. During the colonoscopy, two pinch biopsies of healthy, normal appearing mucosa were obtained from the descending colon. A fasting blood sample was also collected. The methylation status of {LINE}-1 (long interspersed nuclear element-1) repetitive sequences, as a surrogate measure of global methylation, was quantified in {DNA} extracted from normal colon mucosa and blood leukocytes. Statistical analysis of the relationship between global {DNA} methylation and adenoma risk was conducted on 317 participants, 108 subjects with at least one pathologically confirmed adenoma and 209 subjects with a normal colonoscopy.Results: A statistically significant inverse relationship was observed between {LINE}-1 methylation in colon tissue {DNA} and adenoma risk for males and for both sexes combined for the lowest methylation quartile compared to the highest (adjusted {ORs} = 2.94 and 2.26 respectively). For blood, although the overall pattern of odds ratio estimates was towards an increase in risk for lower methylation quartiles compared to the highest methylation quartile, there were no statistically significant relationships observed. A moderate correlation was found between {LINE}-1 methylation levels measured in tissue and blood (Pearson correlation 0.36).Conclusions: We observed that lower levels of {LINE}-1 {DNA} methylation in normal appearing background colon mucosa were associated with increased adenoma risk for males, and for both sexes combined. Though these findings provide some support for a relationship between {LINE}-1 {DNA} methylation in colon mucosal tissue and adenoma risk, large prospective cohort studies are needed to confirm results. Until such investigations are done, the clinical usefulness of {LINE}-1 methylation as a biomarker of increased adenoma risk is uncertain. Regardless, this study contributes to a better understanding of the role of global {DNA} methylation as an early event in {CR} carcinogenesis with implications for future etiologic research. {\copyright} 2014 King et al.},
    author = {King and Ashbury and Taylor and Tse and Pang and Louw and Vanner},
    citeulike-article-id = {13477174},
    citeulike-linkout-0 = {http://dx.doi.org/10.1186/1471-2407-14-488},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84903676214\&\#38;partnerID=40\&\#38;md5=5203fb30a008550077186b37e68f6e07},
    doi = {10.1186/1471-2407-14-488},
    journal = {{BMC} Cancer},
    keywords = {1, adenoma, adult, aged, article, assessment, biological, blood, cancer, carcinogenesis, cell, clinical, colon, colonoscopy, colorectal, controlled, cross-sectional, difference, dna, element, extraction, female, human, interspersed, leukocyte, long, major, male, marker, methylation, mucosa, nuclear, risk, sampling, sequence, sex, study, tissue, *file-import-15-01-07},
    note = {cited By 0},
    number = {1},
    posted-at = {2015-01-07 18:50:41},
    priority = {2},
    title = {A cross-sectional study of global {DNA} methylation and risk of colorectal adenoma},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84903676214\&partnerID=40\&md5=5203fb30a008550077186b37e68f6e07},
    volume = {14},
    year = {2014}
    }
  • [DOI] Yao, Robinson, Zucchi, Robbins, Babenko, Kovalchuk, Kovalchuk, Olson, and Metz, “Ancestral exposure to stress epigenetically programs preterm birth risk and adverse maternal and newborn outcomes,” BMC medicine, vol. 12, iss. 1, 2014.
    [Bibtex]
    @article{yao_ancestral_2014,
    abstract = {Background: Chronic stress is considered to be one of many causes of human preterm birth ({PTB}), but no direct evidence has yet been provided. Here we show in rats that stress across generations has downstream effects on endocrine, metabolic and behavioural manifestations of {PTB} possibly via {microRNA} ({miRNA}) regulation. Methods: Pregnant dams of the parental generation were exposed to stress from gestational days 12 to 18. Their pregnant daughters (F1) and grand-daughters (F2) either were stressed or remained as non-stressed controls. Gestational length, maternal gestational weight gain, blood glucose and plasma corticosterone levels, litter size and offspring weight gain from postnatal days 1 to 30 were recorded in each generation, including F3. Maternal behaviours were analysed for the first hour after completed parturition, and offspring sensorimotor development was recorded on postnatal day (P) 7. F0 through F2 maternal brain frontal cortex, uterus and placenta {miRNA} and gene expression patterns were used to identify stress-induced epigenetic regulatory pathways of maternal behaviour and pregnancy maintenance.Results: Progressively up to the F2 generation, stress gradually reduced gestational length, maternal weight gain and behavioural activity, and increased blood glucose levels. Reduced offspring growth and delayed behavioural development in the stress cohort was recognizable as early as P7, with the greatest effect in the F3 offspring of transgenerationally stressed mothers. Furthermore, stress altered {miRNA} expression patterns in the brain and uterus of F2 mothers, including the {miR}-200 family, which regulates pathways related to brain plasticity and parturition, respectively. Main {miR}-200 family target genes in the uterus, Stat5b, Zeb1 and Zeb2, were downregulated by multigenerational stress in the F1 generation. Zeb2 was also reduced in the stressed F2 generation, suggesting a causal mechanism for disturbed pregnancy maintenance. Additionally, stress increased placental {miR}-181a, a marker of human {PTB}. Conclusions: The findings indicate that a family history of stress may program central and peripheral pathways regulating gestational length and maternal and newborn health outcomes in the maternal lineage. This new paradigm may model the origin of many human {PTB} causes.},
    author = {Yao and Robinson and Zucchi and Robbins and Babenko and Kovalchuk and Kovalchuk and Olson and Metz},
    citeulike-article-id = {13477173},
    citeulike-linkout-0 = {http://dx.doi.org/10.1186/s12916-014-0121-6},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84905911703\&\#38;partnerID=40\&\#38;md5=eb5766c31eebc587a59ca572eefa1a37},
    doi = {10.1186/s12916-014-0121-6},
    journal = {{BMC} Medicine},
    keywords = {141, 181a, 182, 183, 2, 200, 200a, 200b, 200c, 23b, 429, 451, 96, activity, age, animal, article, behavior, birth, blood, body, cell, control, controlled, cortex, corticosterone, down, drug, environmental, epigenetic, experiment, exposure, expression, factor, female, frontal, gain, gene, gestational, glucose, labor, level, litter, maternal, micro, microrna, motor, nerve, nonhuman, outcome, perinatal, period, placenta, plasticity, pregnancy, premature, prenatal, progeny, protein, rat, reduction, regulation, repression, risk, rna, size, stat5b, stress, study, targeting, third, transcription, trimester, unclassified, uterus, weight, zeb, zeb1, *file-import-15-01-07},
    note = {cited By 2},
    number = {1},
    posted-at = {2015-01-07 18:50:41},
    priority = {2},
    title = {{Ancestral exposure to stress epigenetically programs preterm birth risk and adverse maternal and newborn outcomes}},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84905911703\&partnerID=40\&md5=eb5766c31eebc587a59ca572eefa1a37},
    volume = {12},
    year = {2014}
    }
  • [DOI] Tallen and Riabowol, “Keep-ING balance: tumor suppression by epigenetic regulation,” FEBS letters, vol. 588, iss. 16, pp. 2728-2742, 2014.
    [Bibtex]
    @article{tallen_keep-ing_2014,
    abstract = {Cancer cells accumulate genetic and epigenetic changes that alter gene expression to drive tumorigenesis. Epigenetic silencing of tumor suppressor, cell cycle, differentiation and {DNA} repair genes contributes to neoplastic transformation. The {ING} (inhibitor of growth) proteins ({ING}1-{ING}5) have emerged as a versatile family of growth regulators, phospholipid effectors, histone mark sensors and core components of {HDAC}1/2 - and several {HAT} chromatin-modifying complexes. This review will describe the characteristic pathways by which {ING} family proteins differentially affect the Hallmarks of Cancer and highlight the various epigenetic mechanisms by which they regulate gene expression. Finally, we will discuss their potentials as biomarkers and therapeutic targets in epigenetic treatment strategies. {\copyright} 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.},
    author = {Tallen and Riabowol},
    citeulike-article-id = {13477172},
    citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.febslet.2014.03.011},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84905123233\&\#38;partnerID=40\&\#38;md5=26c21de592ebec41d5abf289a549e9e4},
    doi = {10.1016/j.febslet.2014.03.011},
    journal = {{FEBS} Letters},
    keywords = {acetylation, acetyltransferase, acid, activity, acyltransferase, aging, amino, animals, biological, cancer, complex, data, deacetylase, disease, down, drug, enzyme, epigenesis, epigenetic, epigenetics, factor, formation, function, gene, genetic, histone, homeodomain, human, humans, ing, ing-protein, ing1, ing2, ing3, ing4, ing5, inhibition, interaction, journal, malignant, marker, membrane, methylation, molecular, motif, mutation, myst, neoplasms, neoplastic, nonhuman, oncogene, pathogenesis, phosphorylation, priority, processing, protein, proteins, regulation, renaissance, review, sequence, signal, sin3a, structure, suppression, suppressor, targeting, tertiary, therapy, transcription, transduction, tumor, unclassified, upregulation, *file-import-15-01-07},
    note = {cited By 1},
    number = {16},
    pages = {2728--2742},
    posted-at = {2015-01-07 18:50:41},
    priority = {2},
    title = {Keep-{ING} balance: Tumor suppression by epigenetic regulation},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84905123233\&partnerID=40\&md5=26c21de592ebec41d5abf289a549e9e4},
    volume = {588},
    year = {2014}
    }
  • [DOI] Volodko, Gordon, Salla, Ghazaleh, and Baksh, “RASSF tumor suppressor gene family: biological functions and regulation,” FEBS letters, vol. 588, iss. 16, pp. 2671-2684, 2014.
    [Bibtex]
    @article{volodko_rassf_2014,
    abstract = {Genetic changes through allelic loss and nucleic acid or protein modifications are the main contributors to loss of function of tumor suppressor proteins. In particular, epigenetic silencing of genes by promoter hypermethylation is associated with increased tumor severity and poor survival. The {RASSF} (Ras association domain family) family of proteins consists of 10 members, many of which are tumor suppressor proteins that undergo loss of expression through promoter methylation in numerous types of cancers such as leukemia, melanoma, breast, prostate, neck, lung, brain, colorectal and kidney cancers. In addition to their tumor suppressor function, {RASSF} proteins act as scaffolding agents in microtubule stability, regulate mitotic cell division, modulate apoptosis, control cell migration and cell adhesion, and modulate {NFκB} activity and the duration of inflammation. The ubiquitous functions of these proteins highlight their importance in numerous physiological pathways. In this review, we will focus on the biological roles of the {RASSF} family members and their regulation. {\copyright} 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.},
    author = {Volodko and Gordon and Salla and Ghazaleh and Baksh},
    citeulike-article-id = {13477171},
    citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.febslet.2014.02.041},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84905120617\&\#38;partnerID=40\&\#38;md5=8f62c99560f01892e453843823eed35d},
    doi = {10.1016/j.febslet.2014.02.041},
    journal = {{FEBS} Letters},
    keywords = {1, 10, 1a, 1c, 2, 3, 4, 5, 6, 7, 8, 9, alpha, animals, apoptosis, association, atm, beta, bowel, c, cancer, carcinogenesis, catenin, cell, chronic, colitis, complex, cpg, cycle, cyclin, cytosine, damage, daxx, death, degradation, dependent, disease, dna, domain, drug, epigenesis, epigenetics, expression, factor, family, fkhr, formation, function, gene, genetic, heart, histone, homology, human, humans, hypertrophy, inducing, inflammation, inflammatory, inhibition, interaction, interleukin, island, journal, kinase, ligand, localization, mechanism, methylation, methylcytosine, methyltransferase, microrna, micrornas, microtubule, modification, necrosis, nfb, oncogene, p27, pax3, phosphorylation, post-translational, priority, processing, proliferation, promoter, protein, proteins, ras, rassf, region, regulation, regulatory, related, review, sequence, signal, silencing, stability, structure, suppressor, targeting, transcription, transduction, tubulin, tumor, unclassified, unindexed, ventricle, *file-import-15-01-07},
    note = {cited By 0},
    number = {16},
    pages = {2671--2684},
    posted-at = {2015-01-07 18:50:41},
    priority = {2},
    title = {{RASSF} tumor suppressor gene family: Biological functions and regulation},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84905120617\&partnerID=40\&md5=8f62c99560f01892e453843823eed35d},
    volume = {588},
    year = {2014}
    }
  • [DOI] B. Wang, D. Li, A. Kovalchuk, D. Litvinov, and O. Kovalchuk, “Ionizing radiation-inducible miR-27b suppresses leukemia proliferation via targeting cyclin a2,” International journal of radiation oncology biology physics, vol. 90, iss. 1, pp. 53-62, 2014.
    [Bibtex]
    @article{wang_ionizing_2014,
    abstract = {Purpose Ionizing radiation is a common carcinogen that is important for the development of leukemia. However, the underlying epigenetic mechanisms remain largely unknown. The goal of the study was to explore {microRNAome} alterations induced by ionizing radiation ({IR}) in murine thymus, and to determine the role of {IR}-inducible {microRNA} ({miRNA}/{miR}) in the development of leukemia. Methods and Materials We used the well-established C57BL/6 mouse model and {miRNA} microarray profiling to identify {miRNAs} that are differentially expressed in murine thymus in response to irradiation. {TIB}152 human leukemia cell line was used to determine the role of estrogen receptor-α ({ERα}) in {miR}-27b transcription. The biological effects of ectopic {miR}-27b on leukemogenesis were measured by western immunoblotting, cell viability, apoptosis, and cell cycle analyses. Results Here, we have shown that {IR} triggers the differential expression of {miR}-27b in murine thymus tissue in a dose-, time- and sex-dependent manner. {miR}-27b was significantly down-regulated in leukemia cell lines {CCL}119 and {TIB}152. Interestingly, {ERα} was overexpressed in those 2 cell lines, and it was inversely correlated with {miR}-27b expression. Therefore, we used {TIB}152 as a model system to determine the role of {ERα} in {miR}-27b expression and the contribution of {miR}-27b to leukemogenesis. β-Estradiol caused a rapid and transient reduction in {miR}-27b expression reversed by either {ERα}-neutralizing antibody or {ERK}1/2 inhibitor. Ectopic expression of {miR}-27b remarkably suppressed {TIB}152 cell proliferation, at least in part, by inducing S-phase arrest. In addition, it attenuated the expression of cyclin A2, although it had no effect on the levels of {PCNA}, {PPARγ}, {CDK}2, p21, p27, p-p53, and cleaved caspase-3. Conclusion Our data reveal that β-estradiol/{ERα} signaling may contribute to the down-regulation of {miR}-27b in acute leukemia cell lines through the {ERK}1/2 pathway, and that {miR}-27b may function as a tumor suppressor that inhibits cell proliferation by targeting cyclin A2. {\copyright} 2014 Elsevier Inc. All rights reserved.},
    author = {Wang, B. and Li, D. and Kovalchuk, A. and Litvinov, D. and Kovalchuk, O.},
    citeulike-article-id = {13477170},
    citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.ijrobp.2014.04.055},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84905916834\&\#38;partnerID=40\&\#38;md5=8317ee46bbb8b828547f63e211eed5d2},
    doi = {10.1016/j.ijrobp.2014.04.055},
    journal = {International Journal of Radiation Oncology Biology Physics},
    keywords = {2, 27b, 3, a2, activated, activity, alpha, analysis, and, animal, animals, antibodies, apoptosis, article, biological, c57bl, caspase, cell, cells, checkpoint, checkpoints, controlled, course, culture, cycle, cyclin, cycline, death, dependent, differential, disease, diseases, dose-response, down, down-regulation, drug, ectopic, epigenetic, estradiol, estrogen, experiment, expression, expressions, factors, female, gamma, gland, human, humans, inbred, ionizing, journal, kinase, leukemia, leukemogenesis, line, male, materials, mechanisms, methods, mice, microarrays, microrna, micrornas, model, mouse, neutralizing, nonhuman, p21, p27, p53, peroxisome, phase, priority, proliferation, proliferator, protein, radiation, radiation-induced, receptor, receptors, reduction, regulation, relationship, response, rna, s, sex, shielding, study, thymus, time, tissue, transcription, transient, tumor, unclassified, viability, *file-import-15-01-07},
    note = {cited By 0},
    number = {1},
    pages = {53--62},
    posted-at = {2015-01-07 18:50:40},
    priority = {2},
    title = {Ionizing radiation-inducible {miR}-27b suppresses leukemia proliferation via targeting cyclin A2},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84905916834\&partnerID=40\&md5=8317ee46bbb8b828547f63e211eed5d2},
    volume = {90},
    year = {2014}
    }
  • [DOI] Nguyen, Stechishin, Luchman, Lun, Senger, Robbins, Cairncross, and Weiss, “Novel MSH6 mutations in treatment-na\ive glioblastoma and anaplastic oligodendroglioma contribute to temozolomide resistance independently of MGMT promoter methylation,” Clinical cancer research, vol. 20, iss. 18, pp. 4894-4903, 2014.
    [Bibtex]
    @article{nguyen_novel_2014,
    abstract = {Purpose: The current standard of care for glioblastoma ({GBM}) involves a combination of surgery, radiotherapy, and temozolomide chemotherapy, but this regimen fails to achieve long-term tumor control. Resistance to temozolomide is largely mediated by expression of the {DNA} repair enzyme {MGMT}; however, emerging evidence suggests that inactivation of {MSH}6 and other mismatch repair proteins plays an important role in temozolomide resistance. Here, we investigate endogenous {MSH}6 mutations in {GBM}, anaplastic oligodendroglial tumor tissue, and corresponding brain tumor-initiating cell lines ({BTIC}). Experimental Design: {MSH}6 sequence and {MGMT} promoter methylation were determined in human tumor samples and {BTICs}. Sensitivity to temozolomide was evaluated in vitro using {BTICs} in the absence and presence of O6-benzylguanine to deplete {MGMT}. The influence of {MGMT} and {MSH}6 status on in vivo sensitivity to temozolomide was evaluated using intracranial {BTIC} xenografts. Results: We identified 11 previously unreported mutations in {MSH}6 in nine different glioma samples and six paired {BTIC} lines from adult patients. In addition, {MSH}6 mutations were documented in three oligodendrogliomas and two treatment-nave gliomas, both previously unreported findings. These mutations were found to influence the sensitivity of {BTICs} to temozolomide both in vitro and in vivo, independent of {MGMT} promoter methylation status. Conclusions: These data demonstrate that {endogenousMSH}6mutations may be present before alkylator therapy and occur in at least two histologic subtypes of adult glial neoplasms, with this report serving as the first to note these mutations in oligodendroglioma. These findings broaden our understanding of the clinical response to temozolomide in gliomas.},
    author = {Nguyen and Stechishin and Luchman and Lun and Senger and Robbins and Cairncross and Weiss},
    citeulike-article-id = {13477169},
    citeulike-linkout-0 = {http://dx.doi.org/10.1158/1078-0432.CCR-13-1856},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84907426055\&\#38;partnerID=40\&\#38;md5=d20b79cf348781dda80766a5fa5ed895},
    doi = {10.1158/1078-0432.CCR-13-1856},
    journal = {Clinical Cancer Research},
    keywords = {*file-import-15-01-07},
    note = {cited By 0},
    number = {18},
    pages = {4894--4903},
    posted-at = {2015-01-07 18:50:40},
    priority = {2},
    title = {Novel {MSH}6 mutations in treatment-na\{i}ve glioblastoma and anaplastic oligodendroglioma contribute to temozolomide resistance independently of {MGMT} promoter methylation},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84907426055\&partnerID=40\&md5=d20b79cf348781dda80766a5fa5ed895},
    volume = {20},
    year = {2014}
    }

2013

  • N. Raghuram, H. Strickfaden, D. McDonald, K. Williams, H. Fang, C. Mizzen, J. J. Hayes, J. Th’ng, and M. J. Hendzel, “Pin1 promotes histone H1 dephosphorylation and stabilizes its binding to chromatin,” J. cell biol., vol. 203, iss. 1, pp. 57-71, 2013.
    [Bibtex]
    @Article{pmid24100296,
    Author="Raghuram, N. and Strickfaden, H. and McDonald, D. and Williams, K. and Fang, H. and Mizzen, C. and Hayes, J. J. and Th'ng, J. and Hendzel, M. J. ",
    Title="{{P}in1 promotes histone {H}1 dephosphorylation and stabilizes its binding to chromatin}",
    Journal="J. Cell Biol.",
    Year="2013",
    Volume="203",
    Number="1",
    Pages="57--71",
    Month="Oct",
    Abstract={Histone H1 plays a crucial role in stabilizing higher order chromatin structure. Transcriptional activation, DNA replication, and chromosome condensation all require changes in chromatin structure and are correlated with the phosphorylation of histone H1. In this study, we describe a novel interaction between Pin1, a phosphorylation-specific prolyl isomerase, and phosphorylated histone H1. A sub-stoichiometric amount of Pin1 stimulated the dephosphorylation of H1 in vitro and modulated the structure of the C-terminal domain of H1 in a phosphorylation-dependent manner. Depletion of Pin1 destabilized H1 binding to chromatin only when Pin1 binding sites on H1 were present. Pin1 recruitment and localized histone H1 phosphorylation were associated with transcriptional activation independent of RNA polymerase II. We thus identify a novel form of histone H1 regulation through phosphorylation-dependent proline isomerization, which has consequences on overall H1 phosphorylation levels and the stability of H1 binding to chromatin.},
    Note={[PubMed Central:\href{http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798258}{PMC3798258}] [DOI:\href{http://dx.doi.org/10.1083/jcb.201305159}{10.1083/jcb.201305159}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/24100296}{24100296}] }
    }
  • M. J. Hendzel and R. A. Greenberg, “Conversations between chromatin modifications and DNA double strand break repair: a commentary,” Mutat. res., vol. 750, iss. 1-2, pp. 1-4, 2013.
    [Bibtex]
    @Article{pmid23994712,
    Author="Hendzel, M. J. and Greenberg, R. A. ",
    Title="{{C}onversations between chromatin modifications and {D}{N}{A} double strand break repair: a commentary}",
    Journal="Mutat. Res.",
    Year="2013",
    Volume="750",
    Number="1-2",
    Pages="1--4",
    Month="Oct",
    Note={[PubMed Central:\href{http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3827952}{PMC3827952}] [DOI:\href{http://dx.doi.org/10.1016/j.mrfmmm.2013.08.003}{10.1016/j.mrfmmm.2013.08.003}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/23994712}{23994712}] }
    }
  • K. L. Conn, M. J. Hendzel, and L. M. Schang, “The differential mobilization of histones H3.1 and H3.3 by herpes simplex virus 1 relates histone dynamics to the assembly of viral chromatin,” Plos pathog., vol. 9, iss. 10, p. e1003695, 2013.
    [Bibtex]
    @Article{pmid24130491,
    Author="Conn, K. L. and Hendzel, M. J. and Schang, L. M. ",
    Title="{{T}he differential mobilization of histones {H}3.1 and {H}3.3 by herpes simplex virus 1 relates histone dynamics to the assembly of viral chromatin}",
    Journal="PLoS Pathog.",
    Year="2013",
    Volume="9",
    Number="10",
    Pages="e1003695",
    Abstract={During lytic infections, HSV-1 genomes are assembled into unstable nucleosomes. The histones required for HSV-1 chromatin assembly, however, are in the cellular chromatin. We have shown that linker (H1) and core (H2B and H4) histones are mobilized during HSV-1 infection, and proposed that the mobilized histones are available for assembly into viral chromatin. However, the actual relevance of histone mobilization remained unknown. We now show that canonical H3.1 and variant H3.3 are also mobilized during HSV-1 infection. Mobilization required no HSV-1 protein expression, although immediate early or early proteins enhanced it. We used the previously known differential association of H3.3 and H3.1 with HSV-1 DNA to test the relevance of histone mobilization. H3.3 binds to HSV-1 genomes first, whereas H3.1 only binds after HSV-1 DNA replication initiates. Consistently, H3.3 and H3.1 were differentially mobilized. H3.1 mobilization decreased with HSV-1 DNA replication, whereas H3.3 mobilization was largely unaffected by it. These results support a model in which previously mobilized H3.1 is immobilized by assembly into viral chromatin during HSV-1 DNA replication, whereas H3.3 is mobilized and assembled into HSV-1 chromatin throughout infection. The differential mobilizations of H3.3 and H3.1 are consistent with their differential assembly into viral chromatin. These data therefore relate nuclear histone dynamics to the composition of viral chromatin and provide the first evidence that histone mobilization relates to viral chromatin assembly.},
    Note={[PubMed Central:\href{http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795045}{PMC3795045}] [DOI:\href{http://dx.doi.org/10.1371/journal.ppat.1003695}{10.1371/journal.ppat.1003695}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/24130491}{24130491}] }
    }
  • K. L. Conn, M. J. Hendzel, and L. M. Schang, “The differential mobilization of histones H3.1 and H3.3 by herpes simplex virus 1 relates histone dynamics to the assembly of viral chromatin,” Plos pathog., vol. 9, iss. 10, p. e1003695, 2013.
    [Bibtex]
    @Article{pmid24130491,
    Author="Conn, K. L. and Hendzel, M. J. and Schang, L. M. ",
    Title="{{T}he differential mobilization of histones {H}3.1 and {H}3.3 by herpes simplex virus 1 relates histone dynamics to the assembly of viral chromatin}",
    Journal="PLoS Pathog.",
    Year="2013",
    Volume="9",
    Number="10",
    Pages="e1003695",
    Abstract={During lytic infections, HSV-1 genomes are assembled into unstable nucleosomes. The histones required for HSV-1 chromatin assembly, however, are in the cellular chromatin. We have shown that linker (H1) and core (H2B and H4) histones are mobilized during HSV-1 infection, and proposed that the mobilized histones are available for assembly into viral chromatin. However, the actual relevance of histone mobilization remained unknown. We now show that canonical H3.1 and variant H3.3 are also mobilized during HSV-1 infection. Mobilization required no HSV-1 protein expression, although immediate early or early proteins enhanced it. We used the previously known differential association of H3.3 and H3.1 with HSV-1 DNA to test the relevance of histone mobilization. H3.3 binds to HSV-1 genomes first, whereas H3.1 only binds after HSV-1 DNA replication initiates. Consistently, H3.3 and H3.1 were differentially mobilized. H3.1 mobilization decreased with HSV-1 DNA replication, whereas H3.3 mobilization was largely unaffected by it. These results support a model in which previously mobilized H3.1 is immobilized by assembly into viral chromatin during HSV-1 DNA replication, whereas H3.3 is mobilized and assembled into HSV-1 chromatin throughout infection. The differential mobilizations of H3.3 and H3.1 are consistent with their differential assembly into viral chromatin. These data therefore relate nuclear histone dynamics to the composition of viral chromatin and provide the first evidence that histone mobilization relates to viral chromatin assembly.},
    Note={[PubMed Central:\href{http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795045}{PMC3795045}] [DOI:\href{http://dx.doi.org/10.1371/journal.ppat.1003695}{10.1371/journal.ppat.1003695}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/24130491}{24130491}] }
    }
  • K. L. Conn and L. M. Schang, “Chromatin dynamics during lytic infection with herpes simplex virus 1,” Viruses, vol. 5, iss. 7, pp. 1758-1786, 2013.
    [Bibtex]
    @Article{pmid23863878,
    Author="Conn, K. L. and Schang, L. M. ",
    Title="{{C}hromatin dynamics during lytic infection with herpes simplex virus 1}",
    Journal="Viruses",
    Year="2013",
    Volume="5",
    Number="7",
    Pages="1758--1786",
    Month="Jul",
    Abstract={Latent HSV-1 genomes are chromatinized with silencing marks. Since 2004, however, there has been an apparent inconsistency in the studies of the chromatinization of the HSV-1 genomes in lytically infected cells. Nuclease protection and chromatin immunoprecipitation assays suggested that the genomes were not regularly chromatinized, having only low histone occupancy. However, the chromatin modifications associated with transcribed and non-transcribed HSV-1 genes were those associated with active or repressed transcription, respectively. Moreover, the three critical HSV-1 transcriptional activators all had the capability to induce chromatin remodelling, and interacted with critical chromatin modifying enzymes. Depletion or overexpression of some, but not all, chromatin modifying proteins affected HSV-1 transcription, but often in unexpected manners. Since 2010, it has become clear that both cellular and HSV-1 chromatins are highly dynamic in infected cells. These dynamics reconcile the weak interactions between HSV-1 genomes and chromatin proteins, detected by nuclease protection and chromatin immunoprecipitation, with the proposed regulation of HSV-1 gene expression by chromatin, supported by the marks in the chromatin in the viral genomes and the abilities of the HSV-1 transcription activators to modulate chromatin. It also explains the sometimes unexpected results of interventions to modulate chromatin remodelling activities in infected cells.},
    Note={[PubMed Central:\href{http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3738960}{PMC3738960}] [DOI:\href{http://dx.doi.org/10.3390/v5071758}{10.3390/v5071758}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/23863878}{23863878}] }
    }
  • R. Xiang, M. Ghanipoor-Samami, W. H. Johns, T. Eindorf, D. L. Rutley, Z. A. Kruk, C. J. Fitzsimmons, D. A. Thomsen, C. T. Roberts, B. M. Burns, G. I. Anderson, P. L. Greenwood, and S. Hiendleder, “Maternal and paternal genomes differentially affect myofibre characteristics and muscle weights of bovine fetuses at midgestation,” Plos one, vol. 8, iss. 1, p. e53402, 2013.
    [Bibtex]
    @Article{pmid23341941,
    Author="Xiang, R. and Ghanipoor-Samami, M. and Johns, W. H. and Eindorf, T. and Rutley, D. L. and Kruk, Z. A. and Fitzsimmons, C. J. and Thomsen, D. A. and Roberts, C. T. and Burns, B. M. and Anderson, G. I. and Greenwood, P. L. and Hiendleder, S. ",
    Title="{{M}aternal and paternal genomes differentially affect myofibre characteristics and muscle weights of bovine fetuses at midgestation}",
    Journal="PLoS ONE",
    Year="2013",
    Volume="8",
    Number="1",
    Pages="e53402",
    Abstract={Postnatal myofibre characteristics and muscle mass are largely determined during fetal development and may be significantly affected by epigenetic parent-of-origin effects. However, data on such effects in prenatal muscle development that could help understand unexplained variation in postnatal muscle traits are lacking. In a bovine model we studied effects of distinct maternal and paternal genomes, fetal sex, and non-genetic maternal effects on fetal myofibre characteristics and muscle mass. Data from 73 fetuses (Day153, 54% term) of four genetic groups with purebred and reciprocal cross Angus and Brahman genetics were analyzed using general linear models. Parental genomes explained the greatest proportion of variation in myofibre size of Musculus semitendinosus (80-96%) and in absolute and relative weights of M. supraspinatus, M. longissimus dorsi, M. quadriceps femoris and M. semimembranosus (82-89% and 56-93%, respectively). Paternal genome in interaction with maternal genome (P<0.05) explained most genetic variation in cross sectional area (CSA) of fast myotubes (68%), while maternal genome alone explained most genetic variation in CSA of fast myofibres (93%, P<0.01). Furthermore, maternal genome independently (M. semimembranosus, 88%, P<0.0001) or in combination (M. supraspinatus, 82%; M. longissimus dorsi, 93%; M. quadriceps femoris, 86%) with nested maternal weight effect (5-6%, P<0.05), was the predominant source of variation for absolute muscle weights. Effects of paternal genome on muscle mass decreased from thoracic to pelvic limb and accounted for all (M. supraspinatus, 97%, P<0.0001) or most (M. longissimus dorsi, 69%, P<0.0001; M. quadriceps femoris, 54%, P<0.001) genetic variation in relative weights. An interaction between maternal and paternal genomes (P<0.01) and effects of maternal weight (P<0.05) on expression of H19, a master regulator of an imprinted gene network, and negative correlations between H19 expression and fetal muscle mass (P<0.001), suggested imprinted genes and miRNA interference as mechanisms for differential effects of maternal and paternal genomes on fetal muscle.},
    Note={[PubMed Central:\href{http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544898}{PMC3544898}] [DOI:\href{http://dx.doi.org/10.1371/journal.pone.0053402}{10.1371/journal.pone.0053402}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/23341941}{23341941}] }
    }
  • L. C. Young, D. W. McDonald, and M. J. Hendzel, “Kdm4b histone demethylase is a DNA damage response protein and confers a survival advantage following γ-irradiation,” J. biol. chem., vol. 288, iss. 29, pp. 21376-21388, 2013.
    [Bibtex]
    @Article{pmid23744078,
    Author="Young, L. C. and McDonald, D. W. and Hendzel, M. J. ",
    Title="{{K}dm4b histone demethylase is a {D}{N}{A} damage response protein and confers a survival advantage following γ-irradiation}",
    Journal="J. Biol. Chem.",
    Year="2013",
    Volume="288",
    Number="29",
    Pages="21376--21388",
    Month="Jul",
    Abstract={DNA damage evokes a complex and highly coordinated DNA damage response (DDR) that is integral to the suppression of genomic instability. Double-strand breaks (DSBs) are considered the most deleterious form damage. Evidence suggests that trimethylation of histone H3 lysine 9 (H3K9me3) presents a barrier to DSB repair. Also, global levels of histone methylation are clinically predictive for several tumor types. Therefore, demethylation of H3K9 may be an important step in the repair of DSBs. The KDM4 subfamily of demethylases removes H3K9 tri- and dimethylation and contributes to the regulation of cellular differentiation and proliferation; mutation or aberrant expression of KDM4 proteins has been identified in several human tumors. We hypothesize that members of the KDM4 subfamily may be components of the DDR. We found that Kdm4b-enhanced GFP (EGFP) and KDM4D-EGFP were recruited rapidly to DNA damage induced by laser micro-irradiation. Focusing on the clinically relevant Kdm4b, we found that recruitment was dependent on poly(ADP-ribose) polymerase 1 activity as well as Kdm4b demethylase activity. The Kdm4 proteins did not measurably accumulate at γ-irradiation-induced γH2AX foci. Nevertheless, increased levels of Kdm4b were associated with decreased numbers of γH2AX foci 6 h after irradiation as well as increased cell survival. Finally, we found that levels of H3K9me2 and H3K9me3 were decreased at early time points after 2 gray of γ-irradiation. Taken together, these data demonstrate that Kdm4b is a DDR protein and that overexpression of Kdm4b may contribute to the failure of anti-cancer therapy that relies on the induction of DNA damage.},
    Note={[PubMed Central:\href{http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774405}{PMC3774405}] [DOI:\href{http://dx.doi.org/10.1074/jbc.M113.491514}{10.1074/jbc.M113.491514}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/23744078}{23744078}] }
    }
  • L. C. Young and M. J. Hendzel, “The oncogenic potential of Jumonji D2 (JMJD2/KDM4) histone demethylase overexpression,” Biochem. cell biol., vol. 91, iss. 6, pp. 369-377, 2013.
    [Bibtex]
    @Article{pmid24219278,
    Author="Young, L. C. and Hendzel, M. J. ",
    Title="{{T}he oncogenic potential of {J}umonji {D}2 ({J}{M}{J}{D}2/{K}{D}{M}4) histone demethylase overexpression}",
    Journal="Biochem. Cell Biol.",
    Year="2013",
    Volume="91",
    Number="6",
    Pages="369--377",
    Month="Dec",
    Abstract={The Jumonji D2 proteins (JMJD2/KDM4) function to demethylate di- and trimethylated (me2/3) histone 3 lysine 9 (H3K9me2/3) and H3K36me3. Knockout mouse models for Kdm4b and Kdm4d have not resulted in gross abnormalities, while mouse models for Kdm4a and Kdm4c have not been reported. However, the KDM4 subfamily of demethylases are overexpressed in several tumor types. Overexpression of KDM4 proteins alters transcription and chromatin remodeling, driving cellular proliferation, anchorage-independent growth, invasion, and migration. Increased proliferation occurs through KDM4-mediated modification of cell cycle timing, as well as through increased numbers of replication forks. Recent evidence also suggests that KDM4C overexpression contributes to the maintenance of a pluripotent state. Together these data suggest that overexpression of KDM4 proteins induces numerous oncogenic effects.},
    Note={[DOI:\href{http://dx.doi.org/10.1139/bcb-2012-0054}{10.1139/bcb-2012-0054}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/24219278}{24219278}] }
    }
  • D. F. Quail, G. M. Siegers, M. Jewer, and L. M. Postovit, “Nodal signalling in embryogenesis and tumourigenesis,” Int. j. biochem. cell biol., vol. 45, iss. 4, pp. 885-898, 2013.
    [Bibtex]
    @Article{pmid23291354,
    Author="Quail, D. F. and Siegers, G. M. and Jewer, M. and Postovit, L. M. ",
    Title="{{N}odal signalling in embryogenesis and tumourigenesis}",
    Journal="Int. J. Biochem. Cell Biol.",
    Year="2013",
    Volume="45",
    Number="4",
    Pages="885--898",
    Month="Apr",
    Abstract={With few exceptions, most cells in adult organisms have lost the expression of stem cell-associated proteins and are instead characterized by tissue-specific gene expression and function. This cell fate specification is dictated spatially and temporally during embryogenesis. It has become increasingly apparent that the elegant and complicated process of cell specification is "undone" in cancer. This may be because cancer cells respond to their microenvironment and mutations by acquiring a more permissive, plastic epigenome, or because cancer cells arise from mutated stem cells. Regardless, these advanced cancer cells must use stem cell-associated proteins to sustain their phenotype. One such protein is Nodal, an embryonic morphogen belonging to the transforming growth factor-β (TGF-β) superfamily. First described in early developmental models, Nodal orchestrates embryogenesis by regulating a myriad of processes, including mesendoderm induction, left-right asymmetry and embryo implantation. Nodal is relatively restricted to embryonic and reproductive cell types and is thus absent from most normal adult tissues. However, recent studies focusing on a variety of malignancies have demonstrated that Nodal expression re-emerges during cancer progression. Moreover, in almost every cancer studied thus far, the acquisition of Nodal expression is associated with increased tumourigenesis, invasion and metastasis. As the list of cancers that express Nodal grows, it is essential that the scientific and medical communities fully understand how this morphogen is regulated in both normal and neoplastic conditions. Herein, we review the literature relating to normal and pathological Nodal signalling. In particular, we emphasize the role that this secreted protein plays during morphogenic events and how it signals to support stem cell maintenance and tumour progression.},
    Note={[DOI:\href{http://dx.doi.org/10.1016/j.biocel.2012.12.021}{10.1016/j.biocel.2012.12.021}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/23291354}{23291354}] }
    }
  • S. Campbell, I. H. Ismail, L. C. Young, G. G. Poirier, and M. J. Hendzel, “Polycomb repressive complex 2 contributes to DNA double-strand break repair,” Cell cycle, vol. 12, iss. 16, pp. 2675-2683, 2013.
    [Bibtex]
    @Article{pmid23907130,
    Author="Campbell, S. and Ismail, I. H. and Young, L. C. and Poirier, G. G. and Hendzel, M. J. ",
    Title="{{P}olycomb repressive complex 2 contributes to {D}{N}{A} double-strand break repair}",
    Journal="Cell Cycle",
    Year="2013",
    Volume="12",
    Number="16",
    Pages="2675--2683",
    Month="Aug",
    Abstract={Polycomb protein histone methyltransferase, enhancer of Zeste homolog 2 (EZH2), is frequently overexpressed in human malignancy and is implicated in cancer cell proliferation and invasion. However, it is largely unknown whether EZH2 has a role in modulating the DNA damage response. Here, we show that polycomb repressive complex 2 (PRC2) is recruited to sites of DNA damage. This recruitment is independent of histone 2A variant X (H2AX) and the PI-3-related kinases ATM and DNA-PKcs. We establish that PARP activity is required for retaining PRC2 at sites of DNA damage. Furthermore, depletion of EZH2 in cells decreases the efficiency of DSB repair and increases sensitivity of cells to gamma-irradiation. These data unravel a crucial role of PRC2 in determining cancer cellular sensitivity following DNA damage and suggest that therapeutic targeting of EZH2 activity might serve as a strategy for improving conventional chemotherapy in a given malignancy.},
    Note={[PubMed Central:\href{http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865057}{PMC3865057}] [DOI:\href{http://dx.doi.org/10.4161/cc.25795}{10.4161/cc.25795}] [PubMed:\href{http://www.ncbi.nlm.nih.gov/pubmed/23907130}{23907130}] }
    }
  • B. Wang, D. Li, and O. Kovalchuk, “P53 ser15 phosphorylation and histone modifications contribute to ir-induced mir-34a transcription in mammary epithelial cells,” Cell cycle, vol. 12, iss. 13, pp. 2073-2083, 2013.
    [Bibtex]
    @ARTICLE{Wang20132073,
    author={Wang, B. and Li, D. and Kovalchuk, O.},
    title={p53 Ser15 phosphorylation and histone modifications contribute to IR-induced miR-34a transcription in mammary epithelial cells},
    journal={Cell Cycle},
    year={2013},
    volume={12},
    number={13},
    pages={2073-2083},
    note={cited By 3},
    url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84879777406&partnerID=40&md5=29d1396b680b4a397b88ec759d8945cd},
    document_type={Article},
    source={Scopus},
    }
  • [DOI] Koch, Metz, and Kovalchuk, “Epigenetics and miRNAs in the diagnosis and treatment of multiple sclerosis,” Trends in molecular medicine, vol. 19, iss. 1, pp. 23-30, 2013.
    [Bibtex]
    @article{koch_epigenetics_2013,
    abstract = {The risk of developing multiple sclerosis ({MS}) depends on both genetic and environmental factors. Although the genetic susceptibility to {MS} has been investigated in great detail, reports describing epigenetic changes in the context of {MS} have only recently appeared. Epigenetic changes to {DNA} influence gene expression without altering the underlying {DNA} sequence. {DNA} methylation, histone modification, and {miRNA}-associated silencing are the three most important epigenetic mechanisms that influence gene expression. In this review, we summarize recent studies investigating epigenetic changes and {miRNA} as biomarkers for diagnosing {MS} and predicting disease course or treatment response. We also discuss how the current studies address important clinical questions and how future studies could be designed to best inform clinical practice. {\copyright} 2012 Elsevier Ltd.},
    author = {Koch and Metz and Kovalchuk},
    citeulike-article-id = {13477235},
    citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.molmed.2012.10.008},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84871716263\&\#38;partnerID=40\&\#38;md5=a1eaca393f18ef79153dd1bbd7566b85},
    doi = {10.1016/j.molmed.2012.10.008},
    journal = {Trends in Molecular Medicine},
    keywords = {a, accuracy, allergic, beta, biological, clinical, diagnostic, dna, effect, encephalomyelitis, epigenesis, epigenetics, expression, gene, genetic, glatiramer, histone, human, humans, interferon, marker, markers, methylation, microrna, micrornas, modification, multiple, natalizumab, nonhuman, nucleosome, practice, regulation, review, sclerosis, sequence, side, transcription, trichostatin, unspecified, *file-import-15-01-07},
    note = {cited By 8},
    number = {1},
    pages = {23--30},
    posted-at = {2015-01-07 18:50:55},
    priority = {2},
    title = {Epigenetics and {miRNAs} in the diagnosis and treatment of multiple sclerosis},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84871716263\&partnerID=40\&md5=a1eaca393f18ef79153dd1bbd7566b85},
    volume = {19},
    year = {2013}
    }
  • [DOI] Koch, Metz, and Kovalchuk, “Epigenetic changes in patients with multiple sclerosis,” Nature reviews neurology, vol. 9, iss. 1, pp. 35-43, 2013.
    [Bibtex]
    @article{koch_epigenetic_2013,
    abstract = {Epigenetic changes influence gene expression without altering the {DNA} sequence. {DNA} methylation, histone modification and {microRNA}-associated post-transcriptional gene silencing are three key epigenetic mechanisms. Multiple sclerosis ({MS}) is a disease of the {CNS} with both inflammatory and neurodegenerative features. Although studies on epigenetic changes in {MS} only began in the past decade, a growing body of literature suggests that epigenetic changes may be involved in the development of {MS}, possibly by mediating the effects of environmental risk factors, such as smoking, vitamin D deficiency and Epstein-Barr virus infection. Such studies are also beginning to deliver important insights into the pathophysiology of {MS}. For example, inflammation and demyelination in relapsing-remitting {MS} may be related to the increased differentiation of T cells toward a T-helper 17 phenotype, which is an important epigenetically regulated pathophysiological mechanism. In progressive {MS}, other epigenetically regulated mechanisms, such as increased histone acetylation and citrullination of myelin basic protein, might exacerbate the disease course. In this Review, we summarize current knowledge on the role of epigenetic changes in the pathophysiology of {MS}. {\copyright} 2013 Macmillan Publishers Limited. All rights reserved.},
    author = {Koch and Metz and Kovalchuk},
    citeulike-article-id = {13477234},
    citeulike-linkout-0 = {http://dx.doi.org/10.1038/nrneurol.2012.226},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84871922920\&\#38;partnerID=40\&\#38;md5=66720bbbc62bcbcbb6001d1cb34b41af},
    doi = {10.1038/nrneurol.2012.226},
    journal = {Nature Reviews Neurology},
    keywords = {activation, agents, barr, basic, cell, chronic, citrulline, course, d, deacetylase, deficiency, demyelination, disease, dna, environmental, epigenesis, epigenetics, epstein, expression, factor, factors, forecasting, gene, gene-environment, genetic, genome, helper-inducer, histone, human, humans, imprinting, infection, inflammation, inflammatory, inhibitor, inhibitors, interaction, journal, locus, lymphocyte, macrophage, mediators, methylation, methyltransferase, microrna, modification, multiple, myelin, neurologic, neurotransmitter, oligonucleotide, oligonucleotides, pathophysiology, phenotype, posttranscriptional, priority, progression, progressive, protein, relapsing-remitting, review, risk, sclerosis, sequence, silencing, smoking, t, t-lymphocytes, th17, virus, vitamin, *file-import-15-01-07},
    note = {cited By 14},
    number = {1},
    pages = {35--43},
    posted-at = {2015-01-07 18:50:54},
    priority = {2},
    title = {{Epigenetic changes in patients with multiple sclerosis}},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84871922920\&partnerID=40\&md5=66720bbbc62bcbcbb6001d1cb34b41af},
    volume = {9},
    year = {2013}
    }
  • [DOI] Belmonte, Kirkbride, Stone, Pelletier, Bui, Yeung, Hashimoto, Fei, Harada, Munoz, Le, Drews, Brady, Goldberg, and Harada, “Comprehensive developmental profiles of gene activity in regions and subregions of the Arabidopsis seed,” Proceedings of the national academy of sciences of the united states of america, vol. 110, iss. 5, p. E435–E444, 2013.
    [Bibtex]
    @article{belmonte_comprehensive_2013,
    abstract = {Seeds are complex structures that consist of the embryo, endosperm, and seed-coat regions that are of different ontogenetic origins, and each region can be further divided into morphologically distinct subregions. Despite the importance of seeds for food, fiber, and fuel globally, little is known of the cellular processes that characterize each subregion or how these processes are integrated to permit the coordinated development of the seed. We profiled gene activity genome-wide in every organ, tissue, and cell type of Arabidopsis seeds from fertilization through maturity. The resulting {mRNA} datasets offer the most comprehensive description of gene activity in seeds with high spatial and temporal resolution, providing unique insights into the function of understudied seed regions. Global comparisons of {mRNA} populations reveal unexpected overlaps in the functional identities of seed subregions. Analyses of coexpressed gene sets suggest that processes that regulate seed size and filling are coordinated across several subregions. Predictions of gene regulatory networks based on the association of transcription factors with enriched {DNA} sequence motifs upstream of coexpressed genes identify regulators of seed development. These studies emphasize the utility of these datasets as an essential resource for the study of seed biology.},
    author = {Belmonte and Kirkbride and Stone and Pelletier and Bui and Yeung and Hashimoto and Fei and Harada and Munoz and Le and Drews and Brady and Goldberg and Harada},
    citeulike-article-id = {13477233},
    citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.1222061110},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84873135198\&\#38;partnerID=40\&\#38;md5=97ed34ad95949a5538ab735a721d264e},
    doi = {10.1073/pnas.1222061110},
    journal = {Proceedings of the National Academy of Sciences of the United States of America},
    keywords = {acid, activity, analysis, arabidopsis, array, article, association, carbon, chain, cluster, degradation, development, developmental, dna, endosperm, expression, fatty, fertilization, fluorescence, fluorescent, gene, genes, genetic, genetically, gluconeogenesis, glycolysis, green, journal, messenger, metabolism, methylation, microscopy, modified, network, nonhuman, nucleotide, oligonucleotide, plant, plants, polymerase, priority, profiling, protein, proteins, reaction, regulation, regulatory, reverse, rna, seed, seeds, sequence, size, synthesis, transcriptase, *file-import-15-01-07},
    note = {cited By 39},
    number = {5},
    pages = {E435--E444},
    posted-at = {2015-01-07 18:50:54},
    priority = {2},
    title = {{Comprehensive developmental profiles of gene activity in regions and subregions of the Arabidopsis seed}},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84873135198\&partnerID=40\&md5=97ed34ad95949a5538ab735a721d264e},
    volume = {110},
    year = {2013}
    }
  • [DOI] Z. Migicovsky and I. Kovalchuk, “Changes to DNA methylation and homologous recombination frequency in the progeny of stressed plants,” Biochemistry and cell biology, vol. 91, iss. 1, pp. 1-5, 2013.
    [Bibtex]
    @article{migicovsky_changes_2013,
    abstract = {Plants undergo changes in response to biotic and abiotic stresses that help them adjust and survive. Some of these changes may even be passed on to progeny and eventually lead to adaptive evolution. Transgenerational changes in response to stress include alterations in {DNA} methylation and changes in homologous recombination frequency ({HRF}). The progeny of plants that were stressed often show elevated {HRF} as well as genomic hypermethylation, although specific loci that are beneficial in times of stress may be hypomethylated. One of the possible mechanisms responsible for passing the memory to the progeny involves small interfering {RNAs}; Dicer-like proteins, {DCL}2 and {DCL}3, are in part required for this process. However, while epigenetic modifications are often present in the untreated progeny of stressed plants, they are not usually sustained for multiple unexposed generations. Still, transgenerational inheritance of such changes has already begun to provide evidence for an important role of epigenetics in enhancing stress resistance. {\copyright} 2013 Published by {NRC} Research Press.},
    author = {Migicovsky, Z. and Kovalchuk, I.},
    citeulike-article-id = {13477232},
    citeulike-linkout-0 = {http://dx.doi.org/10.1139/bcb-2012-0046},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84874861428\&\#38;partnerID=40\&\#38;md5=4d4454875fe52cf472705ddae41c0348},
    doi = {10.1139/bcb-2012-0046},
    journal = {Biochemistry and Cell Biology},
    keywords = {2, 3, 4, abiotic, acids, adaptive, arabidopsis, biochemistry, biotic, cell, comparative, culture, cycle, dicer, dna, drug, effect, environmental, epigenesis, epigenetic, epigenetics, evolution, factor, flower, genetic, genomic, homologous, iii, inheritance, instability, interfering, like, methylation, microrna, modification, nonhuman, nucleic, patterns, physiological, plant, progeny, protein, proteins, radish, recombination, regulation, response, review, ribonuclease, rna, small, stress, study, tomato, transgenerational, unclassified, *file-import-15-01-07},
    note = {cited By 4},
    number = {1},
    pages = {1--5},
    posted-at = {2015-01-07 18:50:54},
    priority = {2},
    title = {Changes to {DNA} methylation and homologous recombination frequency in the progeny of stressed plants},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84874861428\&partnerID=40\&md5=4d4454875fe52cf472705ddae41c0348},
    volume = {91},
    year = {2013}
    }
  • [DOI] Schuurmans and Kurrasch, “Neurodevelopmental consequences of maternal distress: What do we really know?,” Clinical genetics, vol. 83, iss. 2, pp. 108-117, 2013.
    [Bibtex]
    @article{schuurmans_neurodevelopmental_2013,
    abstract = {{A simple internet search of 'maternal stress and pregnancy' turns up hundreds of hits explaining that an adverse intrauterine environment can affect fetal development and potentially lead to various learning, behavioral, and mood disorders in childhood, as well as complex diseases such as obesity and cardiovascular conditions later in life. Indeed, a growing body of literature now links several intrauterine challenges, including maternal obesity and stress, with adverse developmental outcomes in the child. Over the past 5 years, nearly 5000 publications have explored the consequences of maternal distress on young offspring, a marked increase from the 475 published studies over a comparable period 20 years ago. Yet, despite this explosion of research and widespread warnings to pregnant mothers, we still lack a basic understanding of the pathophysiology linking adverse maternal health to the onset of disease in the child, especially regarding how prenatal and perinatal challenges might affect brain development. Recent studies have begun to explore the cellular basis of the abnormal brain cytoarchitecture associated with fetal exposure to intrauterine challenges. Here, our goal is to review the scientific evidence that maternal distress interferes with key neurodevelopmental steps, as an entry point toward mapping the pathophysiology of pre- and perinatal stress on the unborn child's brain. {\copyright} 2012 John Wiley \& Sons A/S. Published by Blackwell Publishing Ltd.}},
    author = {Schuurmans and Kurrasch},
    citeulike-article-id = {13477231},
    citeulike-linkout-0 = {http://dx.doi.org/10.1111/cge.12049},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84872025922\&\#38;partnerID=40\&\#38;md5=222616899ad848823987949f7706e4c7},
    doi = {10.1111/cge.12049},
    journal = {Clinical Genetics},
    keywords = {age, anxiety, brain, cell, delayed, depression, development, differentiation, distress, effects, emotional, epigenesis, epigenetics, exposure, female, fetal, first, genetic, gestational, human, humans, journal, maternal, myelination, nerve, nervous, neural, neurulation, nutrition, perinatal, physiological, pregnancy, prenatal, priority, psychological, review, second, stress, synaptogenesis, system, third, trimester, tube, *file-import-15-01-07},
    note = {cited By 5},
    number = {2},
    pages = {108--117},
    posted-at = {2015-01-07 18:50:54},
    priority = {2},
    title = {{Neurodevelopmental consequences of maternal distress: What do we really know?}},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84872025922\&partnerID=40\&md5=222616899ad848823987949f7706e4c7},
    volume = {83},
    year = {2013}
    }
  • [DOI] Stechishin, Luchman, Ruan, Blough, Nguyen, Kelly, Cairncross, and Weiss, “On-target JAK2/STAT3 inhibition slows disease progression in orthotopic xenografts of human glioblastoma brain tumor stem cells,” Neuro-oncology, vol. 15, iss. 2, pp. 198-207, 2013.
    [Bibtex]
    @article{stechishin_-target_2013,
    abstract = {Glioblastoma multiforme ({GBM}) is characterized by an aggressive clinical course, therapeutic resistance, and striking molecular heterogeneity. {GBMderived} brain tumor stem cells ({BTSCs}) closely model this molecular heterogeneity and likely have a key role in tumor recurrence and therapeutic resistance. Emerging evidence indicates that Janus kinase ({JAK})2/ signal transducer and activator of transcription ({STAT})3 is an important mediator of tumor cell survival, growth, and invasion in a large group of {GBM}. Here, we used a large set of molecularly heterogeneous {BTSCs} to evaluate the translational potential of {JAK}2/{STAT}3 therapeutics. Methods. {BTSCs} were cultured from {GBM} patients and {MGMT} promoter methylation, and the mutation statuses of {EGFR}, {PTEN}, and {TP}53 were determined. Endogenous {JAK}2/{STAT}3 activity was assessed in human {GBM} tissue, {BTSCs}, and orthotopic xenografts by immunohistochemistry and Western blotting. {STAT}3 short hairpin (sh){RNA}, cucurbitacin-I, and {WP}1066 were used to inhibit {JAK}2/{STAT}3 activity in vitro and in vivo. Results. The {JAK}2/{STAT}3 pathway was demonstrated to be highly activated in human {GBM}, molecularly heterogeneous {BTSCs} derived from these tumors, and {BTSC} xenografts. {STAT}3 {shRNA} knockdown or cucurbitacin- I and {WP}1066 administration resulted in on-target {JAK}2/{STAT}3 inhibition and dramatically reduced {BTSC} survival regardless of endogenous {MGMT} promoter methylation or {EGFR}, {PTEN}, and {TP}53 mutational status. {BTSC} orthotopic xenografts maintained the high levels of activated {JAK}2/{STAT}3 seen in their parent human tumors. Intraperitoneal {WP}1066 reduced intratumoral {JAK}2/{STAT}3 activity and prolonged animal survival. Conclusion. Our study demonstrates the in vitro and in vivo efficacy of on-target {JAK}2/{STAT}3 inhibition in heterogeneous {BTSC} lines that closely emulate the genomic and tumorigenic characteristics of human {GBM}.{\copyright} The Author(s) 2012.},
    author = {Stechishin and Luchman and Ruan and Blough and Nguyen and Kelly and Cairncross and Weiss},
    citeulike-article-id = {13477230},
    citeulike-linkout-0 = {http://dx.doi.org/10.1093/neuonc/nos302},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84875757507\&\#38;partnerID=40\&\#38;md5=f12bb3cf3c6ea433e55637834f561051},
    doi = {10.1093/neuonc/nos302},
    journal = {Neuro-Oncology},
    keywords = {1066, 2, 3, 4, 5, aged, animal, animals, antitumor, apoptosis, article, assays, blotting, brain, cancer, cell, cells, controlled, course, cucurbitacin, cultured, cysteine, cytometry, disease, dna, drug, enzyme, enzymes, epidermal, experiment, factor, female, flow, genetic, glioblastoma, growth, human, humans, i, immunoenzyme, immunohistochemistry, inbred, inhibition, inhibitor, interfering, janus, kinase, male, methylases, methylated, methylation, methyltransferase, mice, middle, model, modification, mouse, neoplasms, neoplastic, nod, nonhuman, p53, phosphatase, phosphatidylinositol, phosphohydrolase, progression, proliferation, promoter, protein, proteins, pten, pyridines, receptor, regions, repair, rna, scid, signal, small, stat3, stem, study, suppressor, targeting, techniques, tissue, transcription, transduction, trisphosphate, triterpenes, tumor, tyrphostins, unclassified, western, wp, xenograft, *file-import-15-01-07},
    note = {cited By 18},
    number = {2},
    pages = {198--207},
    posted-at = {2015-01-07 18:50:54},
    priority = {2},
    title = {On-target {JAK}2/{STAT}3 inhibition slows disease progression in orthotopic xenografts of human glioblastoma brain tumor stem cells},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84875757507\&partnerID=40\&md5=f12bb3cf3c6ea433e55637834f561051},
    volume = {15},
    year = {2013}
    }
  • [DOI] Zucchi, Yao, Ward, Ilnytskyy, Olson, Benzies, Kovalchuk, Kovalchuk, and Metz, “Maternal Stress Induces Epigenetic Signatures of Psychiatric and Neurological Diseases in the Offspring,” PLoS ONE, vol. 8, iss. 2, 2013.
    [Bibtex]
    @article{zucchi_maternal_2013,
    abstract = {The gestational state is a period of particular vulnerability to diseases that affect maternal and fetal health. Stress during gestation may represent a powerful influence on maternal mental health and offspring brain plasticity and development. Here we show that the fetal transcriptome, through {microRNA} ({miRNA}) regulation, responds to prenatal stress in association with epigenetic signatures of psychiatric and neurological diseases. Pregnant Long-Evans rats were assigned to stress from gestational days 12 to 18 while others served as handled controls. Gestational stress in the dam disrupted parturient maternal behaviour and was accompanied by characteristic brain {miRNA} profiles in the mother and her offspring, and altered transcriptomic brain profiles in the offspring. In the offspring brains, prenatal stress upregulated {miR}-103, which is involved in brain pathologies, and downregulated its potential gene target Ptplb. Prenatal stress downregulated {miR}-145, a marker of multiple sclerosis in humans. Prenatal stress also upregulated {miR}-323 and {miR}-98, which may alter inflammatory responses in the brain. Furthermore, prenatal stress upregulated {miR}-219, which targets the gene Dazap1. Both {miR}-219 and Dazap1 are putative markers of schizophrenia and bipolar affective disorder in humans. Offspring transcriptomic changes included genes related to development, axonal guidance and neuropathology. These findings indicate that prenatal stress modifies epigenetic signatures linked to disease during critical periods of fetal brain development. These observations provide a new mechanistic association between environmental and genetic risk factors in psychiatric and neurological disease. {\copyright} 2013 Zucchi et al.},
    author = {Zucchi and Yao and Ward and Ilnytskyy and Olson and Benzies and Kovalchuk and Kovalchuk and Metz},
    citeulike-article-id = {13477229},
    citeulike-linkout-0 = {http://dx.doi.org/10.1371/journal.pone.0056967},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84874315348\&\#38;partnerID=40\&\#38;md5=e76381c4ba92df94be07433af5454b04},
    doi = {10.1371/journal.pone.0056967},
    journal = {{PLoS} {ONE}},
    keywords = {103, 145, 219, 323, 98, animal, animals, article, association, base, brain, chain, complications, controlled, dazap1, development, disease, diseases, disorders, dna, drug, epigenesis, epigenetics, experiment, female, gene, genetic, long-evans, male, maternal, mental, microrna, micrornas, nervous, neurologic, newborn, nonhuman, polymerase, pregnancy, prenatal, primers, psychological, ptplb, rat, rats, reaction, real-time, reverse, risk, sequence, stress, study, system, tissue, transcriptase, transcriptome, unclassified, *file-import-15-01-07},
    note = {cited By 22},
    number = {2},
    posted-at = {2015-01-07 18:50:54},
    priority = {2},
    title = {{Maternal Stress Induces Epigenetic Signatures of Psychiatric and Neurological Diseases in the Offspring}},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84874315348\&partnerID=40\&md5=e76381c4ba92df94be07433af5454b04},
    volume = {8},
    year = {2013}
    }
  • [DOI] Rajarajacholan, Thalappilly, and Riabowol, “The ING1a tumor suppressor regulates endocytosis to induce cellular senescence via the rb-e2f pathway,” PLoS biology, vol. 11, iss. 3, 2013.
    [Bibtex]
    @article{rajarajacholan_ing1a_2013,
    abstract = {The {INhibitor} of Growth ({ING}) proteins act as type {II} tumor suppressors and epigenetic regulators, being stoichiometric members of histone acetyltransferase and histone deacetylase complexes. Expression of the alternatively spliced {ING}1a tumor suppressor increases \&gt;10-fold during replicative senescence. {ING}1a overexpression inhibits growth; induces a large flattened cell morphology and the expression of senescence-associated β-galactosidase; increases Rb, p16, and cyclin D1 levels; and results in the accumulation of senescence-associated heterochromatic foci. Here we identify {ING}1a-regulated genes and find that {ING}1a induces the expression of a disproportionate number of genes whose products encode proteins involved in endocytosis. Intersectin 2 ({ITSN}2) is most affected by {ING}1a, being rapidly induced \&gt;25-fold. Overexpression of {ITSN}2 independently induces expression of the p16 and p57KIP2 cyclin-dependent kinase inhibitors, which act to block Rb inactivation, acting as downstream effectors of {ING}1a. {ITSN}2 is also induced in normally senescing cells, consistent with elevated levels of {ING}1a inducing {ITSN}2 as part of a normal senescence program. Inhibition of endocytosis or altering the stoichiometry of endosome components such as Rab family members similarly induces senescence. Knockdown of {ITSN}2 also blocks the ability of {ING}1a to induce a senescent phenotype, confirming that {ITSN}2 is a major transducer of {ING}1a-induced senescence signaling. These data identify a pathway by which {ING}1a induces senescence and indicate that altered endocytosis activates the Rb pathway, subsequently effecting a senescent phenotype. {\copyright} 2013 Rajarajacholan et al.},
    author = {Rajarajacholan and Thalappilly and Riabowol},
    citeulike-article-id = {13477228},
    citeulike-linkout-0 = {http://dx.doi.org/10.1371/journal.pbio.1001502},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84875447786\&\#38;partnerID=40\&\#38;md5=44be0387727de67b0a2930d729f82d4e},
    doi = {10.1371/journal.pbio.1001502},
    journal = {{PLoS} Biology},
    keywords = {2, acetyltransferase, activation, adaptor, aging, and, article, beta-galactosidase, biotinylation, cell, chain, chromatin, controlled, deacetylase, degradation, division, drug, e2f, endocytosis, enzyme, expression, factors, gene, histone, homology, human, humans, immunoblotting, immunoprecipitation, ing1a, intersectin, intracellular, line, localization, nuclear, overexpression, pathway, peptides, phosphorylation, polymerase, protein, proteins, rb, reaction, real-time, regulation, retinoblastoma, senescence, sequence, signal, signaling, stoichiometry, study, suppressor, synthesis, transcription, transduction, transport, tumor, unclassified, upregulation, vesicular, *file-import-15-01-07},
    note = {cited By 4},
    number = {3},
    posted-at = {2015-01-07 18:50:53},
    priority = {2},
    title = {The {ING}1a Tumor Suppressor Regulates Endocytosis to Induce Cellular Senescence Via the Rb-E2F Pathway},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84875447786\&partnerID=40\&md5=44be0387727de67b0a2930d729f82d4e},
    volume = {11},
    year = {2013}
    }
  • [DOI] Bhattacharjee, Banerjee, and Giri, “Role of genomic instability in arsenic-induced carcinogenicity. A review,” Environment international, vol. 53, pp. 29-40, 2013.
    [Bibtex]
    @article{bhattacharjee_role_2013,
    abstract = {Exposure to chronic arsenic toxicity is associated with cancer. Although unstable genome is a characteristic feature of cancer cells, the mechanisms leading to genomic instability in arsenic-induced carcinogenesis are poorly understood. While there are excellent reviews relating to genomic instability in general, there is no comprehensive review presenting the mechanisms involved in arsenic-induced genomic instability. This review was undertaken to present the current state of research in this area and to highlight the major mechanisms that may involved in arsenic-induced genomic instability leading to cancer. Genomic instability is broadly classified into chromosomal instability ({CIN}), primarily associated with mitotic errors; and microsatellite instability ({MIN}), associated with {DNA} level instability. Arsenic-induced genomic instability is essentially multi-factorial in nature and involves molecular cross-talk across several cellular pathways, and is modulated by a number of endogenous and exogenous factors. Arsenic and its metabolites generate oxidative stress, which in turn induces genomic instability through {DNA} damage, irreversible {DNA} repair, telomere dysfunction, mitotic arrest and apoptosis. In addition to genetic alteration; epigenetic regulation through promoter methylation and {miRNA} expression alters gene expression profiling leading to genome more vulnerable and unstable towards cancer risk. Moreover, mutations or silencing of pro-apoptotic genes can lead to genomic instability by allowing survival of damaged cells that would otherwise die. Although a large body of information is now generated regarding arsenic-induced carcinogenesis; further studies exploring genome-wide association, role of environment and diet are needed for a better understanding of the arsenic-induced genomic instability. {\copyright} 2012 Elsevier Ltd.},
    author = {Bhattacharjee and Banerjee and Giri},
    citeulike-article-id = {13477227},
    citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.envint.2012.12.004},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84872202934\&\#38;partnerID=40\&\#38;md5=f759a98e9d48578278606b3a6faae971},
    doi = {10.1016/j.envint.2012.12.004},
    journal = {Environment International},
    keywords = {90, alkylation, alterations, analysis, apoptosis, arrest, arsenic, association, cancer, carcinogen, carcinogenicity, carcinogens, cell, cells, cellular, checkpoint, chemical, chromosomal, chromosome, chromosomes, contamination, cycle, damage, damaged, damages, death, diet, diseases, dna, environmental, epigenetic, epigenetics, exogenous, exposure, expression, factor, factors, g2, gene, genes, genetic, genome, genome-wide, genomic, genomics, heat, human, humans, induced, inheritance, inhibition, instability, interaction, journal, m, methylation, microrna, microsatellite, mitosis, mitotic, molecular, multifactorial, mutation, of, oxidative, paclitaxel, pathology, pathway, phase, pollutants, pollution, priority, pro-apoptotic, profiling, promoter, protein, region, regulation, repair, repeat, research, review, reviews, risk, rna, sequences, shock, short, silencing, stability, state, stress, tandem, telomere, telomeres, toxicity, trioxide, *file-import-15-01-07},
    note = {cited By 13},
    pages = {29--40},
    posted-at = {2015-01-07 18:50:52},
    priority = {2},
    title = {{Role of genomic instability in arsenic-induced carcinogenicity. A review}},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84872202934\&partnerID=40\&md5=f759a98e9d48578278606b3a6faae971},
    volume = {53},
    year = {2013}
    }
  • [DOI] Satpathy, Nabbi, and Riabowol, “RegulatING chromatin regulators: post-translational modification of the ING family of epigenetic regulators,” Biochemical journal, vol. 450, iss. 3, pp. 433-442, 2013.
    [Bibtex]
    @article{satpathy_regulating_2013,
    abstract = {The five human {ING} genes encode at least 15 splicing isoforms, most of which affect cell growth, differentiation and apoptosis through their ability to alter gene expression by epigenetic mechanisms. Since their discovery in 1996, {ING} proteins have been classified as type {II} tumour suppressors on the basis of reports describing their down-regulation and mislocalization in a variety of cancer types. In addition to their regulation by transcriptional mechanisms, understanding the range of {PTMs} (post-translational modifications) of {INGs} is important in understanding how {ING} functions are fine-tuned in the physiological setting and how they add to the repertoire of activities affected by the {INGs}. In the present paper we review the different {PTMs} that have been reported to occur on {INGs}. We discuss the {PTMs} that modulate {ING} function under normal conditions and in response to a variety of stresses.We also describe the {ING} {PTMs} that have been identified by several unbiased {MS}-based {PTM} enrichment techniques and subsequent proteomic analysis. Among the {ING} {PTMs} identified to date, a subset has been characterized for their biological significance and have been shown to affect processes including subcellular localization, interaction with enzymatic complexes and {ING} protein half-life. The present review aims to highlight the emerging role of {PTMs} in regulating {ING} function and to suggest additional pathways and functions where {PTMs} may effect {ING} function. {\copyright} The Authors.},
    author = {Satpathy and Nabbi and Riabowol},
    citeulike-article-id = {13477226},
    citeulike-linkout-0 = {http://dx.doi.org/10.1042/BJ20121632},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84874643157\&\#38;partnerID=40\&\#38;md5=b8158db4956f6845f5851301b8e3f875},
    doi = {10.1042/BJ20121632},
    journal = {Biochemical Journal},
    keywords = {acetylation, and, animals, assembly, biological, cancer, cell, cellular, chromatin, crystal, damage, deacetylase, degradation, development, disassembly, distribution, dna, domain, drug, e3, epigenesis, epigenetics, expression, family, gene, genetic, growth, h3, half, histone, homeodomain, human, humans, immunity, ing, ing1, ing2, ing3, ing4, ing5, inhibitor, innate, interaction, intracellular, journal, karyopherin, life, ligase, lysine, metastasis, methylation, models, motif, multigene, muscle, nonhuman, nuclear, peptides, phosphorylation, post-translational, priority, processing, protein, proteins, proteomics, review, signaling, spermatogenesis, structure, sumoylation, suppressor, therapy, time, tumor, ubiquitin, ubiquitination, unclassified, *file-import-15-01-07},
    note = {cited By 3},
    number = {3},
    pages = {433--442},
    posted-at = {2015-01-07 18:50:52},
    priority = {2},
    title = {{RegulatING} chromatin regulators: Post-translational modification of the {ING} family of epigenetic regulators},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84874643157\&partnerID=40\&md5=b8158db4956f6845f5851301b8e3f875},
    volume = {450},
    year = {2013}
    }
  • Nabbi, Satpathy, and Riabowol, “Demethylating agents as epigenetic anticancer therapeutics,” Current cancer therapy reviews, vol. 9, iss. 1, pp. 24-33, 2013.
    [Bibtex]
    @article{nabbi_demethylating_2013,
    abstract = {{DNA} methylation is an epigenetic phenomenon, which has major effects on gene expression. Increased methylation generally inhibits transcription while hypomethylation is primarily associated with increased transcription. Hypermethylation of tumor suppressor genes occurs frequently in cancer leading to silencing of these growth inhibitory genes. Demethylating agents are a class of anti-cancer drugs which reduce cytosine methylation, promoting transcriptional activation of genes by virtue of reducing methylation in their promoter regions. Most compounds that inhibit methylation are inhibitors of {DNA} methyltransferases ({DNMTs}) that are responsible for methylating cytosine residues on {DNA}. Azacitidine and Decitabine are two such demethylating agents that are approved for use in myelodysplastic syndromes. In this review, we describe the pharmacology of demethylating agents and their use in recent clinical studies. The current literature describing the efficacy of combining these agents with other chemotherapeutics in various types of cancer is also reviewed. {\copyright} 2013 Bentham Science Publishers.},
    author = {Nabbi and Satpathy and Riabowol},
    citeulike-article-id = {13477225},
    citeulike-linkout-0 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84874837537\&\#38;partnerID=40\&\#38;md5=b1305fc578bb9c46a0a935ef290fffda},
    journal = {Current Cancer Therapy Reviews},
    keywords = {1, 2, 3, 5, 98, a, aberration, acute, and, apoptosis, aza, azacitidine, belinostat, bone, bortezomib, cancer, carcinoma, cell, cervix, chemotherapy, chromosome, clinical, colon, colorectal, combination, cycle, cytotoxicity, damage, deoxycytidine, depsipeptide, dermatosis, dna, doxorubicin, drug, efficacy, emesis, epigallocatechin, epigenetics, eruption, expression, febrile, fluorouracil, gallate, gene, granulocytic, human, hydralazine, induced, inhibitor, journal, kidney, large, leukemia, lymphoma, marrow, mechanism, methylation, methyltransferase, mg, multiple, myelodysplastic, myeloma, nausea, neutrophilic, ovary, overall, panniculitis, panobinostat, phase, potentiation, priority, procainamide, response, review, steroid, survival, syndrome, topic, toxicity, treatment, trial, trichostatin, uterine, vomiting, vorinostat, zebularine, *file-import-15-01-07},
    note = {cited By 0},
    number = {1},
    pages = {24--33},
    posted-at = {2015-01-07 18:50:52},
    priority = {2},
    title = {{Demethylating agents as epigenetic anticancer therapeutics}},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84874837537\&partnerID=40\&md5=b1305fc578bb9c46a0a935ef290fffda},
    volume = {9},
    year = {2013}
    }
  • [DOI] Chen, Tran, Rajarajacholan, Thalappilly, and Riabowol, “ING1b-inducible microRNA203 inhibits cell proliferation,” British journal of cancer, vol. 108, iss. 5, pp. 1143-1148, 2013.
    [Bibtex]
    @article{chen_ing1b-inducible_2013,
    abstract = {Background: The {ING} family of type {II} tumour suppressors serve as both epigenetic 'readers' and target histone acetyl transferase ({HAT}) and histone deacetylase ({HDAC}) 'writers' of the epigenetic histone code. The {ING}1 protein has also been implicated in regulating {microRNA} ({miRNA}) levels. In this study, we identify a link between {ING}1b and the {miRNA} epigenetic network. Methods: Primary fibroblasts infected with adenoviruses expressing {GFP} control or {GFP} plus {ING}1b were examined for alterations in {miRNA} profiles using a {miRNA} {PCR} array. Additional experiments confirmed specificity and consequences of altered {miRNA} expression.Results:{MicroRNAs} {miR}-203, {miR}-375, {miR}-449b and {miR}-200c were increased by {ING}1b overexpression. Ectopic expression of {miR}-203 inhibited U2OS and {MDA}-{MB}-231 cancer cell growth, and induced G1 cell cycle arrest in U2OS cells as estimated by flow cytometry. Transfection with {miR}-203 inhibitor reversed the proliferation inhibition induced by {ING}1b in U2OS cells. {CHIP} assays showed that {ING}1b bound to the promoter of {miR}-203. Western blot analyses showed that {CDK}6, c-Abl and Src were downregulated by the transfection of {miR}-203. Conclusion: These results indicate that {ING}1b epigenetically regulates several {miRNAs} including {miR}-203. The several-fold increase in {miR}-203 by {ING}1b might inhibit cancer cell proliferation through coordinate downregulation of {CDK}6, c-Abl and Src. {\copyright} 2013 Cancer Research {UK}. All rights reserved.},
    author = {Chen and Tran and Rajarajacholan and Thalappilly and Riabowol},
    citeulike-article-id = {13477224},
    citeulike-linkout-0 = {http://dx.doi.org/10.1038/bjc.2013.50},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84875460995\&\#38;partnerID=40\&\#38;md5=f88937a1bc2467ac9485e46b927282af},
    doi = {10.1038/bjc.2013.50},
    journal = {British Journal of Cancer},
    keywords = {200c, 203, 375, 449b, adenovirus, and, article, blotting, cancer, cell, chain, controlled, cycle, cytometry, down, drug, enzyme, epigenetics, expression, fibroblast, flow, g1, gene, genetic, human, humans, infection, ing1b, inhibition, intracellular, journal, line, microrna, micrornas, neoplasms, neoplastic, nuclear, peptides, phase, polymerase, priority, proliferation, protein, proteins, reaction, regulation, signaling, study, suppressor, transfection, tumor, unclassified, western, *file-import-15-01-07},
    note = {cited By 4},
    number = {5},
    pages = {1143--1148},
    posted-at = {2015-01-07 18:50:52},
    priority = {2},
    title = {{ING}1b-inducible {microRNA}203 inhibits cell proliferation},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84875460995\&partnerID=40\&md5=f88937a1bc2467ac9485e46b927282af},
    volume = {108},
    year = {2013}
    }
  • [DOI] Yu, Thakur, Leong-Quong, Suzuki, Pang, Bjorge, Riabowol, and Fujita, “Src regulates the activity of the ING1 tumor suppressor,” PLoS ONE, vol. 8, iss. 4, 2013.
    [Bibtex]
    @article{yu_src_2013,
    abstract = {The {INhibitor} of Growth 1 ({ING}1) is stoichiometric member of histone deacetylase ({HDAC}) complexes and functions as an epigenetic regulator and a type {II} tumor suppressor. It impacts cell growth, aging, apoptosis, and {DNA} repair, by affecting chromatin conformation and gene expression. Down regulation and mislocalization of {ING}1 have been reported in diverse tumor types and Ser/Thr phosphorylation has been implicated in both of these processes. Here we demonstrate that both in vitro and in vivo, the tyrosine kinase Src is able to physically associate with, and phosphorylate {ING}1, which results in a nuclear to cytoplasmic relocalization of {ING}1 in cells and a decrease of {ING}1 stability. Functionally, Src antagonizes the ability of {ING}1 to induce apoptosis, most likely through relocalization of {ING}1 and down regulation of {ING}1 levels. These effects were due to both kinase-dependent and kinase-independent properties of Src, and were most apparent at elevated levels of Src expression. These findings suggest that Src may play a major role in regulating {ING}1 levels during tumorigenesis in those cancers in which high levels of Src expression or activity are present. These data represent the first report of tyrosine kinase-mediated regulation of {ING}1 levels and suggest that kinase activation can impact chromatin structure through the {ING}1 epigenetic regulator. {\copyright} 2013 Yu et al.},
    author = {Yu and Thakur and Leong-Quong and Suzuki and Pang and Bjorge and Riabowol and Fujita},
    citeulike-article-id = {13477223},
    citeulike-linkout-0 = {http://dx.doi.org/10.1371/journal.pone.0060943},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84876013481\&\#38;partnerID=40\&\#38;md5=6b78e89663a8c2bdc3c29862b7fc0144},
    doi = {10.1371/journal.pone.0060943},
    journal = {{PLoS} {ONE}},
    keywords = {1, activation, activity, and, apoptosis, article, binding, blotting, carcinogenesis, cell, cellular, controlled, cytoplasm, distribution, down, drug, enzyme, epigenesis, expression, fractionation, gene, genetic, growth, hek293, humans, immunoprecipitation, in, inhibitor, interaction, intracellular, kinase, kinases, line, localization, mechanism, neoplastic, nuclear, of, peptides, phosphorylation, protein, proteins, regulation, regulatory, signal, signaling, src-family, stability, strain, study, suppressor, synthesis, transduction, transformation, transport, tumor, tyrosine, unclassified, vitro, western, *file-import-15-01-07},
    note = {cited By 3},
    number = {4},
    posted-at = {2015-01-07 18:50:52},
    priority = {2},
    title = {Src Regulates the Activity of the {ING}1 Tumor Suppressor},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84876013481\&partnerID=40\&md5=6b78e89663a8c2bdc3c29862b7fc0144},
    volume = {8},
    year = {2013}
    }
  • [DOI] M. Merrifield and O. Kovalchuk, “Epigenetics in radiation biology: A new research frontier,” Frontiers in genetics, vol. 4, iss. {APR}, 2013.
    [Bibtex]
    @article{merrifield_epigenetics_2013,
    abstract = {The number of people that receive exposure to ionizing radiation ({IR}) via occupational, diagnostic, or treatment-related modalities is progressively rising. It is now accepted that the negative consequences of radiation exposure are not isolated to exposed cells or individuals. Exposure to {IR} can induce genome instability in the germline, and is further associated with transgenerational genomic instability in the offspring of exposed males. The exact molecular mechanisms of transgenerational genome instability have yet to be elucidated, although there is support for it being an epigenetically induced phenomenon. This review is centered on the long-term biological effects associated with {IR} exposure, mainly focusing on the epigenetic mechanisms ({DNA} methylation and small {RNAs}) involved in the molecular etiology of {IR}-induced genome instability, bystander and transgenerational effects. Here, we present evidence that {IR}-mediated effects are maintained by epigenetic mechanisms, and demonstrate how a novel, male germline-specific, small {RNA} pathway is posited to play a major role in the epigenetic inheritance of genome instability. {\copyright} 2013 Merrifield and Kovalchuk.},
    author = {Merrifield, M. and Kovalchuk, O.},
    citeulike-article-id = {13477222},
    citeulike-linkout-0 = {http://dx.doi.org/10.3389/fgene.2013.00040},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84876163688\&\#38;partnerID=40\&\#38;md5=5276d431bfa892efad19f6ff73fbba58},
    doi = {10.3389/fgene.2013.00040},
    journal = {Frontiers in Genetics},
    keywords = {*file-import-15-01-07},
    note = {cited By 10},
    number = {{APR}},
    posted-at = {2015-01-07 18:50:52},
    priority = {2},
    title = {{Epigenetics in radiation biology: A new research frontier}},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84876163688\&partnerID=40\&md5=5276d431bfa892efad19f6ff73fbba58},
    volume = {4},
    year = {2013}
    }
  • [DOI] Molavi, Wang, Zak, Gelebart, Belch, and Lai, “Gene methylation and silencing of SOCS3 in mantle cell lymphoma,” British journal of haematology, vol. 161, iss. 3, pp. 348-356, 2013.
    [Bibtex]
    @article{molavi_gene_2013,
    abstract = {The significance of loss of {SOCS}3, a negative regulator of signalling pathways including those of {STAT}3 and {NF}-κB, was examined in mantle cell lymphoma ({MCL}). The protein expression and gene methylation status of {SOCS}3 were detected using immunohistochemistry/Western blots and methylation-specific polymerase chain reaction, respectively. To evaluate its functional importance, {SOCS}3 was restored in two {SOCS}3-negative {MCL} cell lines using a lentiviral vector. Loss of {SOCS}3 protein expression was found in 3/4 {MCL} cell lines and 18/33 (54·5\%) tumours. {SOCS}3 was found consistently methylated in cell lines (3/4) and tumours (7/7) negative for {SOCS}3, and was unmethylated in all {SOCS}3-positive cell line (1/1) and tumours (5/5) examined. Treatment of all three {SOCS}3-negative cell lines with 2′-deoxy-5-azacytidine restored {SOCS}3 expression. {SOCS}3 is biologically important in {MCL}, as lentiviral transfer of {SOCS}3 in {SOCS}3-negative cell lines increased their apoptotic activity, downregulated nuclear factor ({NF})-κB-p65, cyclin D1 ({CCND}1), {BCL}2 and {BCL}-{XL} ({BCL}2L1), and substantially dampened interleukin 10-induced {STAT}3 activation. In 19 patients aged ≤69 years at time of diagnosis, we found that those that carried {SOCS}3-negative tumours showed a trend toward a worse outcome (P = 0·1, log-rank). {\copyright} 2013 Blackwell Publishing Ltd.},
    author = {Molavi and Wang and Zak and Gelebart and Belch and Lai},
    citeulike-article-id = {13477221},
    citeulike-linkout-0 = {http://dx.doi.org/10.1111/bjh.12262},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84876175744\&\#38;partnerID=40\&\#38;md5=7d6e626260b2429d74069a5cb244079d},
    doi = {10.1111/bjh.12262},
    journal = {British Journal of Haematology},
    keywords = {10, 2, 3, 5, activation, aged, apoptosis, article, aza, azacitidine, bcl, binding, blotting, cancer, cell, chain, clinical, controlled, culture, cyclin, cytokine, d1, deoxycytidine, depletion, dna, down, enhancer, enzyme, expression, factor, fusion, gene, genetic, genomic, human, humans, immunoglobulin, immunohistochemistry, interleukin, journal, lentivirus, line, lymphoma, mantle, mantle-cell, methylation, neoplasm, neoplastic, of, outcome, polymerase, priority, prognosis, protein, proteins, reaction, recombinant, regulation, regulatory, rela, signal, signaling, silencing, stat3, study, suppressor, tissue, transcription, transduction, treatment, tumor, vector, vectors, western, xl, *file-import-15-01-07},
    note = {cited By 4},
    number = {3},
    pages = {348--356},
    posted-at = {2015-01-07 18:50:51},
    priority = {2},
    title = {Gene methylation and silencing of {SOCS}3 in mantle cell lymphoma},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84876175744\&partnerID=40\&md5=7d6e626260b2429d74069a5cb244079d},
    volume = {161},
    year = {2013}
    }
  • [DOI] Neri and Bahlis, “Genomic instability in multiple myeloma: Mechanisms and therapeutic implications,” Expert opinion on biological therapy, vol. 13, iss. {SUPPL}.1, p. S69–S82, 2013.
    [Bibtex]
    @article{neri_genomic_2013,
    abstract = {Introduction: Clonal plasma cells in multiple myeloma ({MM}) are typified by their nearly universal aneuploidy and the presence of recurrent chromosomal aberrations reflecting their chromosomal instability. Multiple myeloma is also recognized to be heterogeneous with distinct molecular subgroups. Deep genome sequencing studies have recently revealed an even wider heterogeneity and genomic instability with the identification of a complex mutational landscape and a branching pattern of clonal evolution. Areas covered: Despite the lack of full understanding of the exact mechanisms driving the genomic instability in {MM}, recent observations have correlated these abnormalities with impairments in the {DNA} damage repair machinery as well as epigenetic changes. These mechanisms and the resulting therapeutic implications will be the subject of this review. Expert opinion: By providing growth advantage of the fittest clone and promoting the acquisition of drug resistance, genomic instability is unarguably beneficial to {MM} cells, however, it may also well be its Achilles heal by creating exploitable vulnerabilities. As such, targeting presumptive {DNA} repair defects and other oncogenic addictions represent a promising area of clinical investigation. In particular, by inducing gene or pathway dependencies not present in normal cells, genomic instability can generate targets of contextual synthetic lethality in {MM} cells. {\copyright} 2013 Informa {UK}, Ltd.},
    author = {Neri and Bahlis},
    citeulike-article-id = {13477220},
    citeulike-linkout-0 = {http://dx.doi.org/10.1517/14712598.2013.814637},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84879563322\&\#38;partnerID=40\&\#38;md5=99df22b59c6205d5df268a4e414a170d},
    doi = {10.1517/14712598.2013.814637},
    journal = {Expert Opinion on Biological Therapy},
    keywords = {11, 13, 1q, 5, aberration, aberrations, agents, and, animals, antineoplastic, assembly, breast, cancer, chromatin, chromosome, damage, differentiation, disassembly, dna, e3, epigenesis, exome, expression, factor, gene, genetic, genome, genomic, genotype, heterozygosity, homeostasis, human, humans, hypermutation, instability, karyotype, ligase, loss, methylation, modification, multiple, mutation, myeloma, nucleotide, osteoclast, ovary, point, polymorphism, profiling, protein, reciprocal, recombination, repair, review, single, somatic, telomere, translocation, ubiquitin, vdj, *file-import-15-01-07},
    note = {cited By 2},
    number = {{SUPPL}.1},
    pages = {S69--S82},
    posted-at = {2015-01-07 18:50:50},
    priority = {2},
    title = {{Genomic instability in multiple myeloma: Mechanisms and therapeutic implications}},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84879563322\&partnerID=40\&md5=99df22b59c6205d5df268a4e414a170d},
    volume = {13},
    year = {2013}
    }
  • [DOI] R. Mychasiuk, A. Harker, S. Ilnytskyy, and R. Gibb, “Paternal stress prior to conception alters DNA methylation and behaviour of developing rat offspring,” Neuroscience, vol. 241, pp. 100-105, 2013.
    [Bibtex]
    @article{mychasiuk_paternal_2013,
    abstract = {Although there has been an abundance of research focused on offspring outcomes associated with maternal experiences, there has been limited examination of the relationship between paternal experiences and offspring brain development. As spermatogenesis is a continuous process, experiences that have the ability to alter epigenetic regulation in fathers may actually change developmental trajectories of offspring. The purpose of this study was to examine the effects of paternal stress prior to conception on behaviour and the epigenome of both male and female developing rat offspring. Male Long-Evans rats were stressed for 27 consecutive days and then mated with control female rats. Early behaviour was tested in offspring using the negative geotaxis task and the open field. At P21 offspring were sacrificed and global {DNA} methylation levels in the hippocampus and frontal cortex were analysed. Paternal stress prior to conception altered behaviour of all offspring on the negative geotaxis task, delaying acquisition of the task. In addition, male offspring demonstrated a reduction in stress reactivity in the open field paradigm spending more time than expected in the centre of the open field. Paternal stress also altered {DNA} methylation patterns in offspring at P21, global methylation was reduced in the frontal cortex of female offspring, but increased in the hippocampus of both male and female offspring. The results from this study clearly demonstrate that paternal stress during spermatogenesis can influence offspring behaviour and {DNA} methylation patterns, and these affects occur in a sex-dependent manner. Development takes place in the centre of a complex interaction between maternal, paternal, and environmental influences, which combine to produce the various phenotypes and individual differences that we perceive. {\copyright} 2013 {IBRO}.},
    author = {Mychasiuk, R. and Harker, A. and Ilnytskyy, S. and Gibb, R.},
    citeulike-article-id = {13477219},
    citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.neuroscience.2013.03.025},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84876704706\&\#38;partnerID=40\&\#38;md5=a7a491e7d37fad1baa209f636379382f},
    doi = {10.1016/j.neuroscience.2013.03.025},
    journal = {Neuroscience},
    keywords = {animal, animals, article, behavior, brain, conception, controlled, cortex, dna, epigenetics, experiment, exposure, female, field, frontal, hippocampus, journal, learning, long-evans, male, methylation, modification, nonhuman, open, paternal, performance, priority, progeny, psychological, rat, rats, stress, study, task, tissue, *file-import-15-01-07},
    note = {cited By 4},
    pages = {100--105},
    posted-at = {2015-01-07 18:50:50},
    priority = {2},
    title = {Paternal stress prior to conception alters {DNA} methylation and behaviour of developing rat offspring},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84876704706\&partnerID=40\&md5=a7a491e7d37fad1baa209f636379382f},
    volume = {241},
    year = {2013}
    }
  • [DOI] Kutanzi and Kovalchuk, “Exposure to estrogen and ionizing radiation causes epigenetic dysregulation, activation of mitogen-activated protein kinase pathways, and genome instability in the mammary gland of ACI rats,” Cancer biology and therapy, vol. 14, iss. 7, pp. 564-573, 2013.
    [Bibtex]
    @article{kutanzi_exposure_2013,
    abstract = {The impact of environmental mutagens and carcinogens on the mammary gland has recently received a lot of attention. Among the most generally accepted carcinogenic agents identified as factors that may increase breast cancer incidence are ionizing radiation and elevated estrogen levels. However, the molecular mechanisms of mammary gland aberrations associated with radiation and estrogen exposure still need to be further elucidated, especially the interplay between elevated hormone levels and radiation. Therefore, in the present study, we investigated molecular changes induced in rat mammary gland tissue by estrogen, ionizing radiation, and the combined action of these two carcinogens using a wellestablished {ACI} rat model. We found that continuous exposure of intact female {ACI} rats to elevated levels of estrogen or to both estrogen and radiation resulted in significant hyperproliferative changes in rat mammary glands. In contrast, radiation exposure alone did not induce hyperplasia. Interestingly, despite the obvious disparity in mammary gland morphology, we did not detect significant differences in the levels of genomic methylation among animals exposed to estrogen, radiation, or both agents together. Specifically, we observed a significant global genomic hypomethylation at 6 weeks of exposure. However, by 12 and 18 weeks, the levels of global {DNA} methylation returned to those of agematched controls. We also found that combined exposure to radiation and estrogen significantly altered the levels of histone H3 and H4 methylation and acetylation. Most importantly, we for the first time demonstrated that estrogen and radiation exposure caused a significant induction of p42/44 {MAP} K and p38 pathways that was paralleled by elevated levels of H3S10 phosphorylation, a well-established biomarker of genome and chromosome instability. The precise role of {MAP} K pathways and their inter-relationship with H3S10 phosphorylation and genome instability in mammary gland tissues needs to be explored further. {\copyright} 2013 Landes Bioscience.},
    author = {Kutanzi and Kovalchuk},
    citeulike-article-id = {13477218},
    citeulike-linkout-0 = {http://dx.doi.org/10.4161/cbt.24599},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84881174513\&\#38;partnerID=40\&\#38;md5=e7ee65f7c1fe27253abe1164e34fcc0f},
    doi = {10.4161/cbt.24599},
    journal = {Cancer Biology and Therapy},
    keywords = {1, 3, 3a, acetylation, aci, activated, activation, activity, allocation, animal, animals, antigen, ape, article, beta, binding, biological, breast, cancer, carcinogenesis, cell, chromosomal, controlled, directed, dna, drug, end, enzyme, epigenetics, epigenomics, estrogen, estrogens, excision, experiment, exposure, female, genomic, gland, glands, h3, h4, histone, histones, hyperplasia, immunohistochemistry, inbred, instability, ionizing, joining, kinase, kinases, ku, mammary, map, marker, methylation, methyltransferase, mitogen, mitogen-activated, model, morphology, nibrin, nonhuman, p38, pathways, phosphorylation, polymerase, proliferation, protein, radiation, random, rat, rats, repair, signaling, sprague-dawley, study, system, tissue, unclassified, *file-import-15-01-07},
    note = {cited By 2},
    number = {7},
    pages = {564--573},
    posted-at = {2015-01-07 18:50:50},
    priority = {2},
    title = {Exposure to estrogen and ionizing radiation causes epigenetic dysregulation, activation of mitogen-activated protein kinase pathways, and genome instability in the mammary gland of {ACI} rats},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84881174513\&partnerID=40\&md5=e7ee65f7c1fe27253abe1164e34fcc0f},
    volume = {14},
    year = {2013}
    }
  • [DOI] I. Kovalchuk, P. Walz, J. Thomas, and O. Kovalchuk, “The increased expression of proteins involved in proliferation, DNA repair and DNA methylation in spleen of mice exposed to e. coli o157: h7 lipopolysaccharide,” Environmental and molecular mutagenesis, vol. 54, iss. 6, pp. 421-428, 2013.
    [Bibtex]
    @article{kovalchuk_increased_2013,
    abstract = {Previous research showed that the consumption of heat-killed E. coli O157:H7 bacteria resulted in an increase in the level of {DNA} damage in intestine, liver and spleen cells. We hypothesized that certain bacterial components released from heat-killed bacteria trigger this response. We analysed the possibility that bacterial components [such as lipopolysaccharides ({LPS})] could induce changes in the level of proteins involved in cell proliferation, {DNA} repair and {DNA} methylation in distal spleen tissues of mice. Four-week-old male mice were provided water supplemented with whole heat-killed E. coli O157:H7 bacteria or components of bacteria ({DNA}, {RNA}, proteins and {LPS}). Spleen cells responded to exposure to whole heat-killed bacteria and {LPS} with an alteration in the level of {PCNA} proteins, {DNA} methylation proteins ({DNMT}1, {DNMT}3A, {DNMT}3B, and {MeCP}2) and {DNA} repair proteins ({APE}1 and {KU}70). Other bacterial components analysed in this study mostly did not alter protein expression. The data suggest that {LPS} is a bacterial component capable of inducing molecular changes in na\{i}ve spleen cells of hosts exposed to it. {\copyright} 2013 Wiley Periodicals, Inc.},
    author = {Kovalchuk, I. and Walz, P. and Thomas, J. and Kovalchuk, O.},
    citeulike-article-id = {13477217},
    citeulike-linkout-0 = {http://dx.doi.org/10.1002/em.21787},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84880036436\&\#38;partnerID=40\&\#38;md5=1b4df28847a6d7dc33874ff21e9f909a},
    doi = {10.1002/em.21787},
    journal = {Environmental and Molecular Mutagenesis},
    keywords = {1, 2, 3a, 3b, and, animal, animals, antigen, antigens, apolipoprotein, apyrimidinic, article, bacteria, binding, breakage, c57bl, cell, cells, coli, contamination, controlled, cpg, cycline, cytosine-5--methyltransferase, damage, dna, dna-apurinic, dna-binding, dnmt, e, enzymes, escherichia, experiment, expression, fluid, inbred, intake, ku, lipopolysaccharide, lipopolysaccharides, lyase, male, methyl, methyl-cpg-binding, methylation, methyltransferase, mice, microorganisms, mouse, mus, musculus, nonhuman, nuclear, o157, or, pcna, proliferating, proliferation, protein, proteins, repair, site, spleen, strand, study, tissue, water, *file-import-15-01-07},
    note = {cited By 2},
    number = {6},
    pages = {421--428},
    posted-at = {2015-01-07 18:50:50},
    priority = {2},
    title = {The increased expression of proteins involved in proliferation, {DNA} repair and {DNA} methylation in spleen of mice exposed to E. coli O157: H7 lipopolysaccharide},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84880036436\&partnerID=40\&md5=1b4df28847a6d7dc33874ff21e9f909a},
    volume = {54},
    year = {2013}
    }
  • [DOI] B. Wang, D. Li, and O. Kovalchuk, “P53 ser15 phosphorylation and histone modifications contribute to IR-induced miR-34a transcription in mammary epithelial cells,” Cell cycle, vol. 12, iss. 13, pp. 2073-2083, 2013.
    [Bibtex]
    @article{wang_p53_2013,
    abstract = {Previous studies have demonstrated that {miR}-34a is a direct transcriptional target of tumor suppressor p53 and plays a crucial role in p53-mediated biological processes, such as cell cycle arrest, apoptosis and senescence. However, the role of p53 phosphorylation at Ser15 and histone modifications in ionizing radiation ({IR})-induced {miR}-34a transcription in human mammary epithelial cells remains unknown. The present study showed that {IR} triggers {miR}-34a induction in rat mammary gland tissue and human mammary epithelial cells in a dose- and time-dependent fashion. Gene copy number and {CpG} methylation exhibit no effect on {IR}-inducible {miR}-34a expression, while the levels of phosphorylated p53 at Ser15 are markedly elevated in human mammary epithelial cells 96 h post-{IR}, which correlates with {IR}-inducible {miR}-34a transcription and the p38 {MAPK} pathway. Conversely, suppression of p38 {MAPK} with {SB}239063 inhibits {IR}-induced p53 phosphorylation at Ser15 and {miR}-34a expression in a dose-dependent manner. Our study found that wild-type p53 is enriched at {miR}-34a promoter, and luciferase activity of {miR}-34a promoter reporter is attenuated by either mutant p53 (Ser15Ala) or mutant {miR}-34a promoter. Furthermore, {IR} also triggers phosphorylation, tri-methylation and acetylation of histone H3 and acetylation of histone H4, which correlates with {IR}-inducible {miR}-34a transcription, while {SAHA} potentiates {IR}-inducible {miR}-34a expression. Moreover, acetyl-histone H3 is significantly enriched at {miR}-34a promoter in {IR}-exposed {HMEC} cells. Yet, we show that there is no correlation between {IR}-inducible {miR}-34a expression and {IR}-induced rapid and transient G2/M arrest. In sum, our novel data for the first time demonstrate that {IR}-induced p53 Ser15 phosphorylation via p38 {MAPK} is essential for its functional regulation of {IR}-inducible {miR}-34a transcription in human mammary epithelial cells, and that histone modifications may also play a key role in {IR}-inducible {miR}-34a expression. {\copyright} 2013 Landes Bioscience.},
    author = {Wang, B. and Li, D. and Kovalchuk, O.},
    citeulike-article-id = {13477216},
    citeulike-linkout-0 = {http://dx.doi.org/10.4161/cc.25135},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84879777406\&\#38;partnerID=40\&\#38;md5=29d1396b680b4a397b88ec759d8945cd},
    doi = {10.4161/cc.25135},
    journal = {Cell Cycle},
    keywords = {34a, acetylation, activated, activation, activity, animal, animals, article, base, breast, cell, cells, checkpoints, controlled, cpg, cultured, cycle, dna, dosage, enzyme, epithelial, epithelium, expression, female, g2, gene, genetic, glands, h3, h4, histone, histones, human, humans, ionizing, island, kinase, long-evans, luciferase, mammary, mammography, map, methylation, microrna, micrornas, mir-34a, mitogen, modification, mutant, nonhuman, p38, p53, phase, phosphorylation, post-translational, processing, promoter, protein, radiation, rat, rats, rattus, region, sequence, signaling, study, suppressor, system, tissue, transcription, transcriptional, tumor, type, vorinostat, wild, *file-import-15-01-07},
    note = {cited By 3},
    number = {13},
    pages = {2073--2083},
    posted-at = {2015-01-07 18:50:50},
    priority = {2},
    title = {p53 Ser15 phosphorylation and histone modifications contribute to {IR}-induced {miR}-34a transcription in mammary epithelial cells},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84879777406\&partnerID=40\&md5=29d1396b680b4a397b88ec759d8945cd},
    volume = {12},
    year = {2013}
    }
  • [DOI] I. Kovalchuk, P. Walz, J. Thomas, and O. Kovalchuk, “Genomic instability in liver cells caused by an LPS-induced bystander-like effect,” PLoS ONE, vol. 8, iss. 7, 2013.
    [Bibtex]
    @article{kovalchuk_genomic_2013,
    abstract = {Bacterial infection has been linked to carcinogenesis, however, there is lack of knowledge of molecular mechanisms that associate infection with the development of cancer. We analyzed possible effects of the consumption of heat-killed E. coli O157:H7 cells or its cellular components, {DNA}, {RNA}, protein or lipopolysaccharides ({LPS}) on gene expression in na\{i}ve liver cells. Four week old mice were provided water supplemented with whole heat-killed bacteria or bacterial components for a two week period. One group of animals was sacrificed immediately, whereas another group was allowed to consume uncontaminated tap water for an additional two weeks, and liver samples were collected, post mortem. Liver cells responded to exposure of whole heat-killed bacteria and {LPS} with alteration in γH2AX levels and levels of proteins involved in proliferation, {DNA} methylation ({MeCP}2, {DNMT}1, {DNMT}3A and 3B) or {DNA} repair ({APE}1 and {KU}70) as well as with changes in the expression of genes involved in stress response, cell cycle control and bile acid biosynthesis. Other bacterial components analysed in this study did not lead to any significant changes in the tested molecular parameters. This study suggests that lipopolysaccharides are a major component of Gram-negative bacteria that induce molecular changes within na\{i}ve cells of the host. {\copyright} 2013 Kovalchuk et al.},
    author = {Kovalchuk, I. and Walz, P. and Thomas, J. and Kovalchuk, O.},
    citeulike-article-id = {13477215},
    citeulike-linkout-0 = {http://dx.doi.org/10.1371/journal.pone.0067342},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84879928901\&\#38;partnerID=40\&\#38;md5=6edb7c7cba693e68da903e979d5d1d27},
    doi = {10.1371/journal.pone.0067342},
    journal = {{PLoS} {ONE}},
    keywords = {1, 2, 3a, 3b, acid, animal, animalia, animals, antigen, antigens, ape1, apyrimidinic, article, bacteria, bacterial, bile, binding, bystander, cell, coli, controlled, cpg, cycle, damage, dna, dna-apurinic, dna-binding, drug, effect, escherichia, experiment, exposure, expression, fluid, gene, genomic, h2ax, hepatocytes, histone, histones, instability, intake, ku, lipopolysaccharide, lipopolysaccharides, liver, lyase, male, messenger, methyl, methylation, methyltransferase, mice, microorganisms, mouse, mus, negibacteria, nonhuman, nuclear, nucleic, o157, or, profiling, proliferating, proliferation, protein, proteins, regulation, repair, rna, site, stress, study, synthesis, tap, tissue, unclassified, water, *file-import-15-01-07},
    note = {cited By 1},
    number = {7},
    posted-at = {2015-01-07 18:50:49},
    priority = {2},
    title = {Genomic Instability in Liver Cells Caused by an {LPS}-Induced Bystander-Like Effect},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84879928901\&partnerID=40\&md5=6edb7c7cba693e68da903e979d5d1d27},
    volume = {8},
    year = {2013}
    }
  • [DOI] Conn and Schang, “Chromatin dynamics during lytic infection with herpes simplex virus 1,” Viruses, vol. 5, iss. 7, pp. 1758-1786, 2013.
    [Bibtex]
    @article{conn_chromatin_2013,
    abstract = {Latent {HSV}-1 genomes are chromatinized with silencing marks. Since 2004, however, there has been an apparent inconsistency in the studies of the chromatinization of the {HSV}-1 genomes in lytically infected cells. Nuclease protection and chromatin immunoprecipitation assays suggested that the genomes were not regularly chromatinized, having only low histone occupancy. However, the chromatin modifications associated with transcribed and non-transcribed {HSV}-1 genes were those associated with active or repressed transcription, respectively. Moreover, the three critical {HSV}-1 transcriptional activators all had the capability to induce chromatin remodelling, and interacted with critical chromatin modifying enzymes. Depletion or overexpression of some, but not all, chromatin modifying proteins affected {HSV}-1 transcription, but often in unexpected manners. Since 2010, it has become clear that both cellular and {HSV}-1 chromatins are highly dynamic in infected cells. These dynamics reconcile the weak interactions between {HSV}-1 genomes and chromatin proteins, detected by nuclease protection and chromatin immunoprecipitation, with the proposed regulation of {HSV}-1 gene expression by chromatin, supported by the marks in the chromatin in the viral genomes and the abilities of the {HSV}-1 transcription activators to modulate chromatin. It also explains the sometimes unexpected results of interventions to modulate chromatin remodelling activities in infected cells. {\copyright} 2013 by the authors; licensee {MDPI}, Basel, Switzerland.},
    author = {Conn and Schang},
    citeulike-article-id = {13477214},
    citeulike-linkout-0 = {http://dx.doi.org/10.3390/v5071758},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84880372296\&\#38;partnerID=40\&\#38;md5=cb550acc2e65a8da4e8b1097a90133cd},
    doi = {10.3390/v5071758},
    journal = {Viruses},
    keywords = {1, acetylation, acetyltransferase, after, and, assay, assembly, bmal1, cell, chromatin, clock, deacetylase, depletion, disassembly, dna, drug, dynamics, expression, factor, fluorescence, gene, genetic, genome, h1, h2b, h3, h4, herpes, herpesvirus, histone, host-pathogen, human, humans, immunoprecipitation, interaction, interactions, methylation, molecular, nonhuman, nuclear, nuclease, nucleosome, phosphorylation, photobleaching, protection, protein, recovery, regulation, release, replication, review, simplex, sumo, sumoylation, transcription, transport, ubiquitination, unclassified, viral, virus, *file-import-15-01-07},
    note = {cited By 3},
    number = {7},
    pages = {1758--1786},
    posted-at = {2015-01-07 18:50:49},
    priority = {2},
    title = {{Chromatin dynamics during lytic infection with herpes simplex virus 1}},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84880372296\&partnerID=40\&md5=cb550acc2e65a8da4e8b1097a90133cd},
    volume = {5},
    year = {2013}
    }
  • [DOI] L. C. Young, D. W. McDonald, and M. J. Hendzel, “Kdm4b histone demethylase is a dna damage response protein and confers a survival advantage following γ-irradiation,” Journal of biological chemistry, vol. 288, iss. 29, pp. 21376-21388, 2013.
    [Bibtex]
    @article{young_kdm4b_2013,
    abstract = {Background: The histone demethylase {KDM}4B is overexpressed in several tumor types and is oncogenic upon overexpression. Results: Kdm4b-{EGFP} recruits to {DNA} damage induced by laser micro-irradiation. Kdm4b-{EGFP} overexpression enhanced double-strand break repair and increased survival followingγ-irradiation. Conclusion: Kdm4b enhances the {DNA} damage response. Significance: Kdm4b overexpression may contribute to cytotoxic anti-cancer treatment resistance {\copyright} 2013 by The American Society for Biochemistry and Molecular Biology, Inc.},
    author = {Young, L. C. and McDonald, D. W. and Hendzel, M. J.},
    citeulike-article-id = {13477213},
    citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.M113.491514},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84880557003\&\#38;partnerID=40\&\#38;md5=10ab7be34bcfa72500f120232ce8c97d},
    doi = {10.1074/jbc.M113.491514},
    journal = {Journal of Biological Chemistry},
    keywords = {after, animals, article, ataxia, binding, break, breaks, catalysis, cell, chromatin, chromosomal, controlled, cytotoxic, damage, damages, demethylase, demethylases, determination, differentiation, dna, dna-activated, domain, domain-containing, double, double-stranded, drug, epigenetics, fluorescence, fluorescent, fusion, gamma, gene, green, heterochromatin, histone, histones, human, humans, immunofluorescence, instability, ionizing, irradiation, journal, jumonji, kdm4b, kinase, lasers, line, lysine, membrane, metabolism, methylation, mice, microscopy, modification, mutated, over-expression, overexpression, permeability, photobleaching, polyadp-ribose, polymerases, priority, proliferation, protein, proteins, radiation, rays, recombinant, recovery, regulation, remodeling, repair, response, site, strand, stranded, structure, study, survival, telangiectasia, transport, tumor, unclassified, *file-import-15-01-07},
    note = {cited By 8},
    number = {29},
    pages = {21376--21388},
    posted-at = {2015-01-07 18:50:49},
    priority = {2},
    title = {{Kdm4b histone demethylase is a dna damage response protein and confers a survival advantage following γ-irradiation}},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84880557003\&partnerID=40\&md5=10ab7be34bcfa72500f120232ce8c97d},
    volume = {288},
    year = {2013}
    }
  • [DOI] Huang and Kauffman, “How to escape the cancer attractor: Rationale and limitations of multi-target drugs,” Seminars in cancer biology, vol. 23, iss. 4, pp. 270-278, 2013.
    [Bibtex]
    @article{huang_how_2013,
    abstract = {{The increasingly evident limitations of target-selective cancer therapy has stimulated a flurry of ideas for overcoming the development of resistance and recurrence - the near universal reason for therapy failure from which target-selective drugs are not exempt. A widely proposed approach to conquer therapy resistance is to depart from the myopic focus on individual causal pathways and instead target multiple nodes in the cancer cell's gene regulatory network. However, most ideas rely on a simplistic conceptualization of networks: utilizing solely their topology and treating it as a display of causal interactions, while ignoring the integrated dynamics in state space. Here, we review the more encompassing formal framework of global network dynamics in which cancer cells, like normal cell types, are high-dimensional attractor states. Then therapy is represented by the network perturbation that will promote the exit from such cancer attractors and reentering a normal attractor. We show in this qualitative and accessible discussion how the idea of a quasi-potential landscape and the theory of least-action-path offer a new formal understanding for computing the set of network nodes (molecular targets) that need to be targeted in concert in order to exit the cancer attractor. But targeting cancer cells based on the network configuration of an average cancer cell, however precise, may not suffice to eradicate all tumor cells because of the dynamic non-genetic heterogeneity of cancer cell populations that makes them moving targets and drives the replenishment of the cancer attractor with surviving, non-responsive cells from neighboring abnormal attractors. {\copyright} 2013 Elsevier Ltd.}},
    author = {Huang and Kauffman},
    citeulike-article-id = {13477212},
    citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.semcancer.2013.06.003},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84881087888\&\#38;partnerID=40\&\#38;md5=67151bfae82b17cc9fcaaaf35dfc7f4f},
    doi = {10.1016/j.semcancer.2013.06.003},
    journal = {Seminars in Cancer Biology},
    keywords = {agent, antineoplastic, biology, cancer, cell, computer, conceptual, drug, dynamics, epigenetics, framework, gene, genetic, growth, heterogeneity, human, interaction, model, molecular, mutation, network, nonhuman, phenotypic, plasticity, regulatory, resistance, review, somatic, stability, stochastic, survival, switching, systems, targeting, *file-import-15-01-07},
    note = {cited By 6},
    number = {4},
    pages = {270--278},
    posted-at = {2015-01-07 18:50:49},
    priority = {2},
    title = {{How to escape the cancer attractor: Rationale and limitations of multi-target drugs}},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84881087888\&partnerID=40\&md5=67151bfae82b17cc9fcaaaf35dfc7f4f},
    volume = {23},
    year = {2013}
    }
  • [DOI] Campbell, Ismail, Young, Poirier, and Hendzel, “Polycomb repressive complex 2 contributes to DNA double-strand break repair,” Cell cycle, vol. 12, iss. 16, pp. 2675-2683, 2013.
    [Bibtex]
    @article{campbell_polycomb_2013,
    abstract = {Polycomb protein histone methyltransferase, enhancer of Zeste homolog 2 ({EZH}2), is frequently overexpressed in human malignancy and is implicated in cancer cell proliferation and invasion. However, it is largely unknown whether {EZH}2 has a role in modulating the {DNA} damage response. Here, we show that polycomb repressive complex 2 ({PRC}2) is recruited to sites of {DNA} damage. This recruitment is independent of histone 2A variant X (H2AX) and the {PI}-3-related kinases {AT} M and {DNA}-{PKcs}. We establish that {PAR} P activity is required for retaining {PRC}2 at sites of {DNA} damage. Furthermore, depletion of {EZH}2 in cells decreases the efficiency of {DSB} repair and increases sensitivity of cells to gammairradiation. These data unravel a crucial role of {PRC}2 in determining cancer cellular sensitivity following {DNA} damage and suggest that therapeutic targeting of {EZH}2 activity might serve as a strategy for improving conventional chemotherapy in a given malignancy. {\copyright} 2013 Landes Bioscience.},
    author = {Campbell and Ismail and Young and Poirier and Hendzel},
    citeulike-article-id = {13477211},
    citeulike-linkout-0 = {http://dx.doi.org/10.4161/cc.25795},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84883217456\&\#38;partnerID=40\&\#38;md5=745a90cebace3e92cfd5b0e9a0e37211},
    doi = {10.4161/cc.25795},
    journal = {Cell Cycle},
    keywords = {2, 3, adenine, adenosine, article, assay, atm, break, breaks, c, cancer, cell, chromatin, colony-forming, complex, controlled, damage, dinucleotide, diphosphate, dna, double, double-stranded, epigenetics, expression, ezh2, factor, fluorescence, function, gamma, group, h2a, histone, human, humans, immunoprecipitation, kinase, microscopy, nicotinamide, parp, phosphatidylinositol, polycomb, protein, proteins, radiation, radiosensitivity, repair, repressive, ribosyltransferase, stranded, study, transcription, units, *file-import-15-01-07},
    note = {cited By 2},
    number = {16},
    pages = {2675--2683},
    posted-at = {2015-01-07 18:50:49},
    priority = {2},
    title = {Polycomb repressive complex 2 contributes to {DNA} double-strand break repair},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84883217456\&partnerID=40\&md5=745a90cebace3e92cfd5b0e9a0e37211},
    volume = {12},
    year = {2013}
    }
  • M. R. J. Morris and S. M. Rogers, “Overcoming maladaptive plasticity through plastic compensation,” Current zoology, vol. 59, iss. 4, pp. 526-536, 2013.
    [Bibtex]
    @article{morris_overcoming_2013,
    abstract = {{Most species evolve within fluctuating environments, and have developed adaptations to meet the challenges posed by environmental heterogeneity. One such adaptation is phenotypic plasticity, or the ability of a single genotype to produce multiple environmentally-induced phenotypes. Yet, not all plasticity is adaptive. Despite the renewed interest in adaptive phenotypic plas-ticity and its consequences for evolution, much less is known about maladaptive plasticity. However, maladaptive plasticity is likely an important driver of phenotypic similarity among populations living in different environments. This paper traces four strategies for overcoming maladaptive plasticity that result in phenotypic similarity, two of which involve genetic changes (standing genetic variation, genetic compensation) and two of which do not (standing epigenetic variation, plastic compensation). Plastic compensation is defined as adaptive plasticity overcoming maladaptive plasticity. In particular, plastic compensation may increase the likelihood of genetic compensation by facilitating population persistence. We provide key terms to disentangle these aspects of phenotypic plasticity and introduce examples to reinforce the potential importance of plastic compensation for under-standing evolutionary change. {\copyright} 2013 Current Zoology.}},
    author = {Morris, M. R. J. and Rogers, S. M.},
    citeulike-article-id = {13477210},
    citeulike-linkout-0 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84881538817\&\#38;partnerID=40\&\#38;md5=1cf714c0b680e8d7ca1695e03fab4673},
    journal = {Current Zoology},
    keywords = {*file-import-15-01-07},
    note = {cited By 2},
    number = {4},
    pages = {526--536},
    posted-at = {2015-01-07 18:50:49},
    priority = {2},
    title = {{Overcoming maladaptive plasticity through plastic compensation}},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84881538817\&partnerID=40\&md5=1cf714c0b680e8d7ca1695e03fab4673},
    volume = {59},
    year = {2013}
    }
  • [DOI] Bose, Thakur, Thalappilly, Ahn, Satpathy, Feng, Suzuki, Kim, and Riabowol, “ING1 induces apoptosis through direct effects at the mitochondria,” Cell death and disease, vol. 4, iss. 9, 2013.
    [Bibtex]
    @article{bose_ing1_2013,
    abstract = {The {ING} family of tumor suppressors acts as readers and writers of the histone epigenetic code, affecting {DNA} repair, chromatin remodeling, cellular senescence, cell cycle regulation and apoptosis. The best characterized member of the {ING} family, {ING}1, interacts with the proliferating cell nuclear antigen ({PCNA}) in a {UV}-inducible manner. {ING}1 also interacts with members of the 14-3-3 family leading to its cytoplasmic relocalization. Overexpression of {ING}1 enhances expression of the Bax gene and was reported to alter mitochondrial membrane potential in a p53-dependent manner. Here we show that {ING}1 translocates to the mitochondria of primary fibroblasts and established epithelial cell lines in response to apoptosis inducing stimuli, independent of the cellular p53 status. The ability of {ING}1 to induce apoptosis in various breast cancer cell lines correlates well with its degree of translocation to the mitochondria after {UV} treatment. Endogenous {ING}1 protein specifically interacts with the pro-apoptotic {BCL}2 family member {BAX}, and colocalizes with {BAX} in a {UV}-inducible manner. Ectopic expression of a mitochondria-targeted {ING}1 construct is more proficient in inducing apoptosis than the wild type {ING}1 protein. Bioinformatic analysis of the yeast interactome indicates that yeast {ING} proteins interact with 64 mitochondrial proteins. Also, sequence analysis of {ING}1 reveals the presence of a {BH}3-like domain. These data suggest a model in which stress-induced cytoplasmic relocalization of {ING}1 by 14-3-3 induces {ING}1-{BAX} interaction to promote mitochondrial membrane permeability and represent a paradigm shift in our understanding of {ING}1 function in the cytoplasm and its contribution to apoptosis. {\copyright} 2013 Macmillan Publishers Limited. All rights reserved.},
    author = {Bose and Thakur and Thalappilly and Ahn and Satpathy and Feng and Suzuki and Kim and Riabowol},
    citeulike-article-id = {13477209},
    citeulike-linkout-0 = {http://dx.doi.org/10.1038/cddis.2013.321},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84885007868\&\#38;partnerID=40\&\#38;md5=33ea783d5ccad0701967cd49280ecfad},
    doi = {10.1038/cddis.2013.321},
    journal = {Cell Death and Disease},
    keywords = {2, analysis, and, apoptosis, article, bcl, bcl-2-associated, bh3, binding, bioinformatics, breast, cancer, cell, cells, cerevisiae, controlled, domain, drug, epithelium, expression, fibroblast, growth1, hek293, human, humans, inhibitor, interaction, intracellular, journal, line, localization, mitochondria, mitochondrial, mitochondrion, nuclear, of, p53, peptides, physiological, priority, protein, proteins, radiation, rays, saccharomyces, sequence, signaling, stimulation, stress, study, suppressor, transport, tumor, type, ultraviolet, unclassified, wild, x, yeast, *file-import-15-01-07},
    note = {cited By 4},
    number = {9},
    posted-at = {2015-01-07 18:50:48},
    priority = {2},
    title = {{ING}1 induces apoptosis through direct effects at the mitochondria},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84885007868\&partnerID=40\&md5=33ea783d5ccad0701967cd49280ecfad},
    volume = {4},
    year = {2013}
    }
  • [DOI] L. Luzhna, P. Kathiria, and O. Kovalchuk, “Micronuclei in genotoxicity assessment: From genetics to epigenetics and beyond,” Frontiers in genetics, vol. 4, iss. {JUL}, 2013.
    [Bibtex]
    @article{luzhna_micronuclei_2013,
    abstract = {Micronuclei ({MN}) are extra-nuclear bodies that contain damaged chromosome fragments and/or whole chromosomes that were not incorporated into the nucleus after cell division. {MN} can be induced by defects in the cell repair machinery and accumulation of {DNA} damages and chromosomal aberrations. A variety of genotoxic agents may induce {MN} formation leading to cell death, genomic instability, or cancer development. In this review, the genetic and epigenetic mechanisms of {MN} formation after various clastogenic and aneugenic effects on cell division and cell cycle are described. The knowledge accumulated in literature on cytotoxicity of various genotoxins is precisely reflected and individual sensitivity to {MN} formation due to single gene polymorphisms is discussed. The importance of rapid {MN} scoring with respect to the cytokinesis-block micronucleus assay is also evaluated. {\copyright} 2013 Luzhna, Kathiria and Kovalchuk.},
    author = {Luzhna, L. and Kathiria, P. and Kovalchuk, O.},
    citeulike-article-id = {13477208},
    citeulike-linkout-0 = {http://dx.doi.org/10.3389/fgene.2013.00131},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84883536112\&\#38;partnerID=40\&\#38;md5=3bd87fd88e9d9460f99d5ff4febaaf3f},
    doi = {10.3389/fgene.2013.00131},
    journal = {Frontiers in Genetics},
    keywords = {*file-import-15-01-07},
    note = {cited By 3},
    number = {{JUL}},
    posted-at = {2015-01-07 18:50:48},
    priority = {2},
    title = {{Micronuclei in genotoxicity assessment: From genetics to epigenetics and beyond}},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84883536112\&partnerID=40\&md5=3bd87fd88e9d9460f99d5ff4febaaf3f},
    volume = {4},
    year = {2013}
    }
  • [DOI] Padmanabhan, Jia, Geary-Joo, Wu, Ferguson-Smith, Fung, Bieda, Snyder, Gravel, Cross, and Watson, “Mutation in folate metabolism causes epigenetic instability and transgenerational effects on development,” Cell, vol. 155, iss. 1, pp. 81-93, 2013.
    [Bibtex]
    @article{padmanabhan_mutation_2013,
    abstract = {Summary The importance of maternal folate consumption for normal development is well established, yet the molecular mechanism linking folate metabolism to development remains poorly understood. The enzyme methionine synthase reductase (Mtrr) is necessary for utilization of methyl groups from the folate cycle. We found that a hypomorphic mutation of the mouse Mtrr gene results in intrauterine growth restriction, developmental delay, and congenital malformations, including neural tube, heart, and placental defects. Importantly, these defects were dependent upon the Mtrr genotypes of the maternal grandparents. Furthermore, we observed widespread epigenetic instability associated with altered gene expression in the placentas of wild-type grandprogeny of Mtrr-deficient maternal grandparents. Embryo transfer experiments revealed that Mtrr deficiency in mice lead to two distinct, separable phenotypes: adverse effects on their wild-type daughters' uterine environment, leading to growth defects in wild-type grandprogeny, and the appearance of congenital malformations independent of maternal environment that persist for five generations, likely through transgenerational epigenetic inheritance. {PaperFlick} {\copyright} 2013 Elsevier Inc.},
    author = {Padmanabhan and Jia and Geary-Joo and Wu and Ferguson-Smith and Fung and Bieda and Snyder and Gravel and Cross and Watson},
    citeulike-article-id = {13477207},
    citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.cell.2013.09.002},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84884862385\&\#38;partnerID=40\&\#38;md5=c90c59bad69fc3dafdc32783dc70be8b},
    doi = {10.1016/j.cell.2013.09.002},
    journal = {Cell},
    keywords = {allele, animal, article, blotting, cell, congenital, controlled, crown, defect, development, developmental, disorder, dna, embryo, embryonic, experiment, expression, female, folate, gene, genomic, genotype, grandparent, growth, heart, hyperhomocysteinemia, inheritance, instability, intrauterine, intron, journal, length, male, malformation, mass, messenger, metabolism, methionine, methylation, model, mouse, mutation, neural, nonhuman, phenotype, placenta, priority, progeny, reductase, retardation, rna, rump, sequence, silencing, southern, spectrometry, stem, study, synthase, tandem, tissue, transfer, tube, type, wild, *file-import-15-01-07},
    note = {cited By 23},
    number = {1},
    pages = {81--93},
    posted-at = {2015-01-07 18:50:48},
    priority = {2},
    title = {{Mutation in folate metabolism causes epigenetic instability and transgenerational effects on development}},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84884862385\&partnerID=40\&md5=c90c59bad69fc3dafdc32783dc70be8b},
    volume = {155},
    year = {2013}
    }
  • [DOI] Kelemen, K\. o, Chan, Taghaddos, and Dinu, “Differentially methylated loci distinguish ovarian carcinoma histological types: evaluation of a DNA methylation assay in FFPE tissue,” BioMed research international, vol. 2013, 2013.
    [Bibtex]
    @article{kelemen_differentially_2013,
    abstract = {Epigenomic markers can identify tumor subtypes, but few platforms can accommodate formalin-fixed paraffin-embedded ({FFPE}) tumor tissue. We tested different amounts of bisulfite-converted (bs) {DNA} from six {FFPE} ovarian carcinomas ({OC}) of serous, endometrioid, and clear cell histologies and two {HapMap} constitutional genomes to evaluate the performance of the {GoldenGate} methylation assay. Methylation status at each 1,505 {CpG} site was expressed as β-values. Comparing 400 ng versus 250 ng {bsDNA}, reproducibility of the assay ranged from Spearman r2=0.41 to 0.90, indicating that β-values obtained with a lower {DNA} amount did not always correlate well with the higher amount. Average methylation for the six samples was higher using 250 ng (β-value = 0.45, {SD}=0.29) than with 400 ng (β-value = 0.36, {SD}=0.32). Reproducibility between duplicate {HapMap} samples (r2=0.76 to 0.92) was also variable. Using 400 ng input {bsDNA}, {THBS}2 and {ERG} were differentially methylated across all histologic types and between endometrioid and clear cell types at {\\textless}0.1\% false discovery rate. Methylation did not always correlate with gene expression (r2=-0.70 to 0.15). We found that lower {bsDNA} overestimates methylation, and, using higher {bsDNA} amounts, we confirmed a previous report of higher methylation of {THBS}2 in clear cell {OC}, which could provide new insight into biological pathways that distinguish {OC} histological types. {\copyright} 2013 Linda E. Kelemen et al.},
    author = {Kelemen and K\{o}bel and Chan and Taghaddos and Dinu},
    citeulike-article-id = {13477206},
    citeulike-linkout-0 = {http://dx.doi.org/10.1155/2013/815894},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84885660033\&\#38;partnerID=40\&\#38;md5=b7e26f2b766490af2fbff4f5e579066f},
    doi = {10.1155/2013/815894},
    journal = {{BioMed} Research International},
    keywords = {2, article, cancer, carcinoma, cell, chromosome, clear, clinical, control, controlled, cpg, dna, endometrioid, erg, expression, extraction, factor, female, gene, genetic, genetics, grading, haplotype, histology, human, humans, island, loci, locus, map, metabolism, methylation, neoplasm, neoplasms, neoplastic, ovarian, ovary, pathology, patient, quality, regulation, reproducibility, study, thrombospondin, tissue, transcription, trial, tumor, x, *file-import-15-01-07},
    note = {cited By 0},
    posted-at = {2015-01-07 18:50:48},
    priority = {2},
    title = {Differentially methylated loci distinguish ovarian carcinoma histological types: Evaluation of a {DNA} methylation assay in {FFPE} tissue},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84885660033\&partnerID=40\&md5=b7e26f2b766490af2fbff4f5e579066f},
    volume = {2013},
    year = {2013}
    }
  • [DOI] Cao, Wu, Shi, Chen, Wu, Yang, Tian, Zhu, Chen, Wang, Biddle, and Gu, “Integrated analysis of long noncoding RNA and coding RNA expression in esophageal squamous cell carcinoma,” International journal of genomics, vol. 2013, 2013.
    [Bibtex]
    @article{cao_integrated_2013,
    abstract = {Tumorigenesis is a complex dynamic biological process that includes multiple steps of genetic and epigenetic alterations, aberrant expression of noncoding {RNA}, and changes in the expression profiles of coding genes. We call the collection of those perturbations in genome space the cancer initiatome. Long noncoding {RNAs} ({lncRNAs}) are pervasively transcribed in the genome and they have key regulatory functions in chromatin remodeling and gene expression. Spatiotemporal variation in the expression of {lncRNAs} has been observed in development and disease states, including cancer. A few dysregulated {lncRNAs} have been studied in cancers, but the role of {lncRNAs} in the cancer initiatome remains largely unknown, especially in esophageal squamous cell carcinoma ({ESCC}). We conducted a genome-wide screen of the expression of {lncRNAs} and coding {RNAs} from {ESCC} and matched adjacent nonneoplastic normal tissues. We identified differentially expressed {lncRNAs} and coding {RNAs} in {ESCC} relative to their matched normal tissue counterparts and validated the result using polymerase chain reaction analysis. Furthermore, we identified differentially expressed {lncRNAs} that are co-located and co-expressed with differentially expressed coding {RNAs} in {ESCC} and the results point to a potential interaction between {lncRNAs} and neighboring coding genes that affect ether lipid metabolism, and the interaction may contribute to the development of {ESCC}. These data provide compelling evidence for a potential novel genomic biomarker of esophageal squamous cell cancer. {\copyright} 2013 Wei Cao et al.},
    author = {Cao and Wu and Shi and Chen and Wu and Yang and Tian and Zhu and Chen and Wang and Biddle and Gu},
    citeulike-article-id = {13477205},
    citeulike-linkout-0 = {http://dx.doi.org/10.1155/2013/480534},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84886460207\&\#38;partnerID=40\&\#38;md5=58c890f5f783371f8722aa682858dd5f},
    doi = {10.1155/2013/480534},
    journal = {International Journal of Genomics},
    keywords = {analysis, article, association, biological, carcinoma, cell, chain, chlormethine, coding, drug, esophageal, expression, gene, genetic, human, interactions, journal, junction, long, marker, nucleotide, pilot, polymerase, priority, profiling, reaction, rna, sequence, squamous, study, tissue, transcriptomics, unclassified, unindexed, untranslated, with, *file-import-15-01-07},
    note = {cited By 3},
    posted-at = {2015-01-07 18:50:48},
    priority = {2},
    title = {Integrated analysis of long noncoding {RNA} and coding {RNA} expression in esophageal squamous cell carcinoma},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84886460207\&partnerID=40\&md5=58c890f5f783371f8722aa682858dd5f},
    volume = {2013},
    year = {2013}
    }
  • [DOI] Kakarougkas, Ismail, Klement, Goodarzi, Conrad, Freire, Shibata, Lobrich, and Jeggo, “Opposing roles for 53BP1 during homologous recombination,” Nucleic acids research, vol. 41, iss. 21, pp. 9719-9731, 2013.
    [Bibtex]
    @article{kakarougkas_opposing_2013,
    abstract = {Although {DNA} non-homologous end-joining repairs most {DNA} double-strand breaks ({DSBs}) in G2 phase, late repairing {DSBs} undergo resection and repair by homologous recombination ({HR}). Based on parallels to the situation in G1 cells, previous work has suggested that {DSBs} that undergo repair by {HR} predominantly localize to regions of heterochromatin ({HC}). By using H3K9me3 and H4K20me3 to identify {HC} regions, we substantiate and extend previous evidence, suggesting that {HC}-{DSBs} undergo repair by {HR}. Next, we examine roles for 53BP1 and {BRCA}1 in this process. Previous studies have shown that 53BP1 is pro-non-homologous end-joining and anti-{HR}. Surprisingly, we demonstrate that in G2 phase, 53BP1 is required for {HR} at {HC}-{DSBs} with its role being to promote phosphorylated {KAP}-1 foci formation. {BRCA}1, in contrast, is dispensable for {pKAP}-1 foci formation but relieves the barrier caused by 53BP1. As 53BP1 is retained at irradiation-induced foci during {HR}, we propose that {BRCA}1 promotes displacement but retention of 53BP1 to allow resection and any necessary {HC} modifications to complete {HR}. In contrast to this role for 53BP1 in {HR} in G2 phase, we show that it is dispensable for {HR} in S phase, where {HC} regions are likely relaxed during replication. {\copyright} The Author(s) 2013. Published by Oxford University Press.},
    author = {Kakarougkas and Ismail and Klement and Goodarzi and Conrad and Freire and Shibata and Lobrich and Jeggo},
    citeulike-article-id = {13477204},
    citeulike-linkout-0 = {http://dx.doi.org/10.1093/nar/gkt729},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84890049642\&\#38;partnerID=40\&\#38;md5=6ea5581108c0a97e215d5dc583afd558},
    doi = {10.1093/nar/gkt729},
    journal = {Nucleic Acids Research},
    keywords = {1, acid, animal, animals, article, associated, binding, brca1, break, breaks, cell, cells, chromosomal, controlled, cultured, cycle, dna, dna-activated, dna-binding, domain, double, double-stranded, drug, embryo, end, ester, g2, h3, h4, heterochromatin, histone, homologous, humans, hydroxyurea, joining, journal, kinase, krab, line, mesylic, methyl, mice, mouse, non-histone, nonhuman, p53, phase, phosphorylation, priority, protein, proteins, recombination, recombinational, repair, repressor, s, stranded, study, tumor, unclassified, *file-import-15-01-07},
    note = {cited By 7},
    number = {21},
    pages = {9719--9731},
    posted-at = {2015-01-07 18:50:48},
    priority = {2},
    title = {{Opposing roles for 53BP1 during homologous recombination}},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84890049642\&partnerID=40\&md5=6ea5581108c0a97e215d5dc583afd558},
    volume = {41},
    year = {2013}
    }
  • [DOI] Mychasiuk, Muhammad, Ilnytskyy, and Kolb, “Persistent gene expression changes in NAc, mPFC, and OFC associated with previous nicotine or amphetamine exposure,” Behavioural brain research, vol. 256, pp. 655-661, 2013.
    [Bibtex]
    @article{mychasiuk_persistent_2013,
    abstract = {Highly addictive drugs like nicotine and amphetamine not only change an individual's behaviour in the short and long-term, they also induce persistent changes in neuronal excitability and morphology. Although research has started to examine the epigenetic changes that occur immediately after drug exposure, there has been little investigation into the persistent modifications to the epigenome that likely moderate the stable maintenance of the neurological changes. Male Long-Evans rats were administered amphetamine, nicotine, or saline for 14 consecutive days, given a 14 day withdrawal period, and then sacrificed. {DNA} from the {mPFC}, {OFC}, and nucleus accumbens ({NAc}) was used for global {DNA} methylation analysis and {RNA} from the same brain regions was used for gene expression analysis. Following the two-week withdrawal period, exposure to amphetamine or nicotine was associated with a decrease in global {DNA} methylation in each brain region examined. Previous exposure to nicotine was associated with changes in expression of 16 genes ({NAc}:6, {mPFC}:5, {OFC}:5) whereas exposure to amphetamine was associated with changes in expression of 25 genes ({NAc}:13, {OFC}:8, {mPFC}:4). The persistent epigenetic changes associated with exposure to amphetamine and nicotine were region and drug dependent, and differ from the latent epigenetic changes that occur immediately after drug exposure. The changes in {DNA} methylation are consistent with the gene expression results and provide further support to the notion that {DNA} methylation is the key regulatory mechanism for experience dependent changes. {\copyright} 2013 Elsevier B.V.},
    author = {Mychasiuk and Muhammad and Ilnytskyy and Kolb},
    citeulike-article-id = {13477203},
    citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.bbr.2013.09.006},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84885447576\&\#38;partnerID=40\&\#38;md5=c74d0868cb2a2b807324732744e1ffda},
    doi = {10.1016/j.bbr.2013.09.006},
    journal = {Behavioural Brain Research},
    keywords = {abuse, accumbens, addiction, administration, amphetamine, analysis, animal, animals, article, association, behavior, brain, central, chloride, chronic, controlled, cortex, dependence, dna, drug, epigenesis, epigenetic, epigenetics, experiment, exposure, expression, function, gene, genetic, journal, long-evans, male, mechanics, mechanism, messenger, methylation, model, modification, molecular, nerve, nervous, nicotine, nonhuman, nucleus, orbital, potential, prefrontal, priority, psychomotor, rat, rats, region, regulatory, rna, sequence, sodium, stimulant, stimulants, study, system, tissue, *file-import-15-01-07},
    note = {cited By 1},
    pages = {655--661},
    posted-at = {2015-01-07 18:50:47},
    priority = {2},
    title = {Persistent gene expression changes in {NAc}, {mPFC}, and {OFC} associated with previous nicotine or amphetamine exposure},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84885447576\&partnerID=40\&md5=c74d0868cb2a2b807324732744e1ffda},
    volume = {256},
    year = {2013}
    }
  • [DOI] Karatsoreos, Thaler, Borgland, Champagne, Hurd, and Hill, “Food for thought: Hormonal, experiential, and neural influences on feeding and obesity,” Journal of neuroscience, vol. 33, iss. 45, pp. 17610-17616, 2013.
    [Bibtex]
    @article{karatsoreos_food_2013,
    abstract = {{Obesity is a growing public health problem. Although convenient, the notion that obesity is simply a problem of will power is increasingly antiquated. It is becoming clear that complex interactions of environment, neurohormonal systems, and transgenerational effects directly contribute to obesity. This review highlights data presented at the Society for Neuroscience Annual Meeting in San Diego, California in 2013; and although not meant as an exhaustive review of the area, this reivew will explore seemingly disparate areas of research that, when taken as a whole, illuminate the complex topography of the causes and consequences of obesity. We discuss how disruption of the biological clock, a consequence of modern society, can lead to changes in the brain and periphery that lead to obesity.We explore how obesity can actually cause pathological changes within the hypothalamus of the brain (a key regulator of food intake and metabolic homeostasis). How reward circuitry, particularly the ventral tegmental area, responds to insulin and how these effects modulate feeding and the salience of feeding cues are mechanistically described. We also investigate how nutrition may cross generational boundaries to affect the development and function of offspring, underscoring the long reach of metabolic effects. Finally, the role of the endocannabinoid system is emphasized as a critical node in the transduction of many of these effects. Together, this review should provide perspective into the neural causes and consequences of obesity, and hopefully lead to new areas of interdisciplinary research to tackle this important public health epidemic. {\copyright} 2013 the authors.}},
    author = {Karatsoreos and Thaler and Borgland and Champagne and Hurd and Hill},
    citeulike-article-id = {13477202},
    citeulike-linkout-0 = {http://dx.doi.org/10.1523/JNEUROSCI.3452-13.2013},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84887079546\&\#38;partnerID=40\&\#38;md5=00f4677f141e28de50d19d6ae9d55511},
    doi = {10.1523/JNEUROSCI.3452-13.2013},
    journal = {Journal of Neuroscience},
    keywords = {1, acid, amidase, animals, appetite, arcuate, article, barrier, behavior, biological, blood, brain, caloric, cannabinoid, cholecystokinin, dopamine, endocannabinoid, energy, epigenetics, fatty, feeding, food, function, ghrelin, gliosis, glucose, homeostasis, hormonal, human, humans, inflammation, insulin, intake, journal, leptin, metabolic, neuroprotection, nonhuman, nucleus, obesity, potentiometry, priority, proopiomelanocortin, receptor, regulation, reward, rhythm, syndrome, tegmentum, ventral, x, *file-import-15-01-07},
    note = {cited By 3},
    number = {45},
    pages = {17610--17616},
    posted-at = {2015-01-07 18:50:47},
    priority = {2},
    title = {{Food for thought: Hormonal, experiential, and neural influences on feeding and obesity}},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84887079546\&partnerID=40\&md5=00f4677f141e28de50d19d6ae9d55511},
    volume = {33},
    year = {2013}
    }
  • [DOI] Villota-Herdoiza, Pila, Quiniou, Waldbieser, and Magor, “Transcriptional regulation of teleost Aicda genes. Part 1 – Suppressors of promiscuous promoters,” Fish and shellfish immunology, vol. 35, iss. 6, pp. 1981-1987, 2013.
    [Bibtex]
    @article{villota-herdoiza_transcriptional_2013,
    abstract = {In order to better understand antibody affinity maturation in fishes we sought to identify gene regulatory elements that could drive expression of activated B-cell specific fluorescent reporter transgenes in zebrafish. Specifically the promoter and several non-coding regions of the channel catfish (Ictalurus punctatus) and zebrafish (Danio rerio) were tested for transcriptional activity using a dual luciferase reporter system in transfected fish leukocytes and two mammalian cell lines that constitutively express Aicda (activation-induced cytidine deaminase). The promoters of both fish Aicda genes were as transcriptionally active as an {SV}40 promoter control in all cell lines tested, regardless of the cells ability to express Aicda. Coupling of a putative intron 1 enhancer or a region 10kb upstream of the zebrafish promoter effectively silenced transcription from the fish Aicda promoter. Paradoxically these suppressor elements enhanced transcription when they were coupled to the mouse Aicda intron 1 enhancer. The results are considered in context of similar observations for Aicda transcriptional regulation in mice and in light of recent evidence that Aicda is utilized for epigenetic reprogramming of several non-lymphoid cell types. {\copyright} 2013 Elsevier Ltd.},
    author = {Villota-Herdoiza and Pila and Quiniou and Waldbieser and Magor},
    citeulike-article-id = {13477201},
    citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.fsi.2013.09.035},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84888432937\&\#38;partnerID=40\&\#38;md5=685ef0d4fbc5246007104fdae1e5fe71},
    doi = {10.1016/j.fsi.2013.09.035},
    journal = {Fish and Shellfish Immunology},
    keywords = {40, activation, activation-induced, aicda, analysis, animal, animals, article, cell, cytidine, danio, data, deaminase, dna, enhancer, expression, fish, gene, genes, genetic, genetics, ictaluridae, ictalurus, induced, intron, introns, line, luciferase, luciferases, mammalia, metabolism, mice, molecular, mouse, mus, nucleotide, pisces, promoter, protein, proteins, punctatus, region, regions, regulation, reporter, rerio, sequence, simian, teleostei, transcription, transfection, transgene, transgenes, virus, zebra, zebrafish, *file-import-15-01-07},
    note = {cited By 0},
    number = {6},
    pages = {1981--1987},
    posted-at = {2015-01-07 18:50:47},
    priority = {2},
    title = {{Transcriptional regulation of teleost Aicda genes. Part 1 - Suppressors of promiscuous promoters}},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84888432937\&partnerID=40\&md5=685ef0d4fbc5246007104fdae1e5fe71},
    volume = {35},
    year = {2013}
    }
  • [DOI] L. C. Young and M. J. Hendzel, “The oncogenic potential of jumonji d2 (JMJD2/KDM4) histone demethylase overexpression,” Biochemistry and cell biology, vol. 91, iss. 6, pp. 369-377, 2013.
    [Bibtex]
    @article{young_oncogenic_2013,
    abstract = {The Jumonji D2 proteins ({JMJD}2/{KDM}4) function to demethylate di-and trimethylated (me2/3) histone 3 lysine 9 (H3K9me2/3) and H3K36me3. Knockout mouse models for Kdm4b and Kdm4d have not resulted in gross abnormalities, while mouse models for Kdm4a and Kdm4c have not been reported. However, the {KDM}4 subfamily of demethylases are overexpressed in several tumor types. Overexpression of {KDM}4 proteins alters transcription and chromatin remodeling, driving cellular proliferation, anchorage-independent growth, invasion, and migration. Increased proliferation occurs through {KDM}4-mediated modification of cell cycle timing, as well as through increased numbers of replication forks. Recent evidence also suggests that {KDM}4C overexpression contributes to the maintenance of a pluripotent state. Together these data suggest that overexpression of {KDM}4 proteins induces numerous oncogenic effects. {\copyright} 2013 Published by {NRC} Research Press.},
    author = {Young, L. C. and Hendzel, M. J.},
    citeulike-article-id = {13477200},
    citeulike-linkout-0 = {http://dx.doi.org/10.1139/bcb-2012-0054},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84880543767\&\#38;partnerID=40\&\#38;md5=dd69b0a0c9d40d90928932d030827d2c},
    doi = {10.1139/bcb-2012-0054},
    journal = {Biochemistry and Cell Biology},
    keywords = {and, animals, assembly, cell, chromatin, cycle, demethylases, disassembly, drosophila, expression, gene, histone, histones, humans, isoenzymes, melanogaster, methylation, mice, neoplasms, neoplastic, regulation, signal, transduction, transformation, transgenic, *file-import-15-01-07},
    note = {cited By 6},
    number = {6},
    pages = {369--377},
    posted-at = {2015-01-07 18:50:47},
    priority = {2},
    title = {The oncogenic potential of Jumonji D2 ({JMJD}2/{KDM}4) histone demethylase overexpression},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84880543767\&partnerID=40\&md5=dd69b0a0c9d40d90928932d030827d2c},
    volume = {91},
    year = {2013}
    }
  • [DOI] G. Wilkinson, D. Dennis, and C. Schuurmans, “Proneural genes in neocortical development,” Neuroscience, vol. 253, pp. 256-273, 2013.
    [Bibtex]
    @article{wilkinson_proneural_2013,
    abstract = {Neurons, astrocytes and oligodendrocytes arise from {CNS} progenitor cells at defined times and locations during development, with transcription factors serving as key determinants of these different neural cell fates. An emerging theme is that the transcription factors that specify {CNS} cell fates function in a context-dependent manner, regulated by post-translational modifications and epigenetic alterations that partition the genome (and hence target genes) into active or silent domains. Here we profile the critical roles of the proneural genes, which encode basic-helix-loop-helix ({bHLH}) transcription factors, in specifying neural cell identities in the developing neocortex. In particular, we focus on the proneural genes Neurogenin 1 (Neurog1), Neurog2 and Achaete scute-like 1 (Ascl1), which are each expressed in a distinct fashion in the progenitor cell pools that give rise to all of the neuronal and glial cell types of the mature neocortex. Notably, while the basic functions of these proneural genes have been elucidated, it is becoming increasingly evident that tight regulatory controls dictate when, where and how they function. Current efforts to better understand how proneural gene function is regulated will not only improve our understanding of neocortical development, but are also critical to the future development of regenerative therapies for the treatment of neuronal degeneration or disease. {\copyright} 2013 {IBRO}.},
    author = {Wilkinson, G. and Dennis, D. and Schuurmans, C.},
    citeulike-article-id = {13477199},
    citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.neuroscience.2013.08.029},
    citeulike-linkout-1 = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84884711305\&\#38;partnerID=40\&\#38;md5=091a306ca8d1349b0b2b1e6908a85e62},
    doi = {10.1016/j.neuroscience.2013.08.029},
    journal = {Neuroscience},
    keywords = {1, 2, 3, a, achaete, achaete-scute, activators, and, animals, as-c, ascl1, astrocyte, baf, basic, basic-helix-loop-helix, beta, bhlh, brahma-associated, brain, catenin, caudal, cell, cells, cge, complex, control, cycle, development, developmental, differentiation, domain, drug, dynamics, eminences, enhancer, expression, factor, factors, fate, fates, function, gaba, gabaergic, gain, ganglionic, gata, gene, genes, genetic, glia, glial, glu, glutamatergic, glycogen, group, gsk3, hairy, helix, helix-loop-helix, hes1, high, hmga, human, humans, interaction, intracellular, journal, kinase, lateral, lge, like, lineage, loop, loss, mash1, maturation, medial, mge, migration, mobility, molecular, mutation, neocortex, nerve, neurog, neurog1, neurog2, neurogenin, neuronal, nicd, nonhuman, notch, of, oligodendrocyte, opcs, pathway, pcg, phase, phosphorylation, polycomb, post-translational, prc, precursor, priority, processing, profiling, proneural, protein, pu, radial, regulation, repressive, review, rgcs, scute, scute-like, selection, serine-proline, signal, signaling, sp, split, stability, stat, stem, subventricular, svz, switching, synthase, telencephalon, transcription, transducers, unclassified, upregulation, ventricular, vz, wnt, zone, *file-import-15-01-07},
    note = {cited By 14},
    pages = {256--273},
    posted-at = {2015-01-07 18:50:46},
    priority = {2},
    title = {{Proneural genes in neocortical development}},
    url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84884711305\&partnerID=40\&md5=091a306ca8d1349b0b2b1e6908a85e62},
    volume = {253},
    year = {2013}
    }