What is Epigenetics?

A growing scientific discipline.

Epigenetics is relatively new, but rapidly growing, scientific discipline that investigates the effect developmental or environmental factors have on how genes are expressed or “turned on” in a way that does not change the underlying DNA sequence. The epigenome is a complex layer of regulatory information superimposed on the genome that includes chromosome structure and DNA methylation.

DNA is an organism’s instruction manual. It tells an organism’s cells how to construct tissues and organs. However, since every cell has the same genetic information, how do certain cells know, for example, to become neurons rather than skin cells? This is an area where epigenetics plays a major role. Epigenetic factors tell cells which pages of its instruction manual (which genes) to read at any given time. Although an organism’s cells have identical genomes each tissue has a unique epigenome (different epigenetic factors) controlling which genes are expressed (turned on). It is these epigenetic factors that instruct a neuron to develop the structure and characteristics it needs to function properly and differently from a skin cell, i.e. a neuron cell expresses genes that help it develop dendrites and axons. These same genes will be turned off in the skin cell. Epigenetic mechanisms are also effected by an organism’s environment. Environmental factors such as diet can alter where epigenetic marks are laid down on the DNA and thereby influence an organism’s long-term health.


Importance:

Epigenetics is everywhere and happening all the time. The collection of epigenetic factors (epigenome) in your cells is affected by the environment, your lifestyle, aging, chemicals and toxins, and diseases. Epigenetic changes can be stable and last a lifetime, and even be passed on to your offspring. These changes can affect your health and wellbeing. However, your epigenome is dynamic and is constantly being affected by your environment, therefore epigenetic changes can be reversed by lifestyle changes or medications. Studies of identical twins, whom have identical DNA, start life with fairly similar epigenomes, but their epigenomes become increasingly different with age (see figure). Because the different environments and lifestyles each are exposed to provide them with unique epigenomes, it is possible for one twin to develop a disease like diabetes or cancer while the other does not.

Reference: http://www.pnas.org/content/102/30/10604.long
Resource: http://learn.genetics.utah.edu/content/epigenetics/twins/


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Biological Molecular Mechanisms

Epigenetics is the study of the biochemical factors or signals that regulate gene expression without changing the underlying sequence of the DNA. The epigenetics factors are often characterized by chemical modifications to DNA (DNA methylation), to the proteins that package DNA (histones), or RNA molecules.

Resources: http://epigenie.com/epigenie-learning-center/epigenetics/epigenetic-regulation/

DNA Methylation occurs when a methyl group is attached to the DNA molecule (at the cytosine base) in order to mark it. When several methyl tags are added to the in front of a gene, the DNA sequence representing the gene cannot be read or expressed. Therefore the DNA methylation acts like a stop sign and turns off gene expression.

Reference: http://www.jbc.org/content/286/21/18347.full

Resource: http://www.whatisepigenetics.com/dna-methylation/

dna methylationJ Mol Cell Biol 2011 Feb 3(1) 51-8, Figure 1

Stretched end to end, human DNA is about 1.8 meters long, far too big to fit into the nucleus of a cell. Therefore, in order to fit, it has to be tightly packaged. Histone proteins are used as spools around which the DNA is wrapped. These wrappings are called nucleosomes. The nucleosomes are further compressed to form chromosomes. If the cell needs to read any piece of DNA wound in a nucleosome, the DNA needs to be unfolded. Epigenetics marks (acetylation) on the histones control how the DNA is wrapped and can release genes for reading, turning gene expression on. Removal of the epigenetic mark can cause the DNA to be wrapped tighter and turn gene expression off.

Reference: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3193420/

Resources: http://epigenie.com/epigenie-learning-center/epigenetics/histone-acetylation-and-genome-function/ , http://www.whatisepigenetics.com/histone-modifications/

491143a-i5.0Histones

 

RNA’s traditional role is to act as a messenger carrying instructions from DNA, it tells the cell how to make proteins and enzymes, but it can also affect and be effected by epigenetic factors. Non-coding RNA (RNA that does not make proteins) and small RNAs have been implicated in several aspects of gene regulation and DNA compaction. Messenger RNA (RNA that makes proteins) can also undergo methylation which will affect how it functions in the in the cell. (more)

Resources: http://www.epibeat.com/category/regulatory-rna/

Epigenetics is relevant to the following areas:

Fetal Development and Early Health: Although the epigenome is susceptible to dysregulation (harmful changes) throughout life, an organism’s epigenome is particularly vulnerable during embryogenesis, which is a period of epigenetic remodeling. Exposure to harmful environmental chemicals can, through epigenetic modifications, lead to developmental disorders and diseases manifesting in childhood, over the life course, or even transgenerationally. For example, epigenetic dysregulation links:

  • early poor nutrition with adult obesity and diabetes,
  • tobacco smoke and air pollution with asthma and developmental delay,
  • toxins like BPA (Bisphenol A) with infertility and cancer risk,
  • PAHs (Polycyclic aromatic hydrocarbons) with neurodevelopmental effects,
  • and childhood stress with anxiety disorders.

Understanding the links between environmental factors and epigenetic changes can help ensure that children into healthy adults.

pregnant_woman

While the child is in utero, environmental factors can affect three generations: the mother, the child and the child’s reproductive cells (his or her offspring). Reprod Toxicol. Apr 2011; 31(3): 363–373.

Reference: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3171169/

Stem Cells: Stem cell-based medicine has tremendous potential to treat a wide range of diseases from cancer to paralysis. Epigenetic modifications play a central role in cell differentiations and limiting differentiated adult cells’ ability to act as stem cells. Understanding the epigenetic modifications that prevent adult (differentiated) cells from acting as stem cells would allow patients to use their own cells for therapeutic measures.

Reference: http://hmg.oxfordjournals.org/content/17/R1/R28.full

Resource: http://www.stemcellresearch.umich.edu/overview/tutorial.html

 

 

 

 

 

 

Development and Aging: Eepigenetic dysregulation can cause a wide range of developmental issues, such as pervasive developmental disorders. Epigenetic changes do not stop in early childhood but continue throughout life and are involved in the aging process. As we age there are large scale changes in the methylation of genes. Furthermore, many age-related DNA methylation biomarkers are associated with disease.

Reference:

http://www.impactaging.com/papers/v2/n2/full/100121.html

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2698247/,http://www.pnas.org/content/109/26/10522.abstract

 

 

 

 

 

Nutrition: Epidemiological studies of famines, such as the Dutch Hunger Winter, have shown that nutrition during early development can impart epigenetic effects that cause lifelong heath issues, such as risk of obesity and diabetes. Studies have also shown that diet and dietary supplements like folic acid and B vitamins can impact the epigenome, reversing epigenetic damage. Alterations in the epigenome can also cause genetically identical organisms to respond differently to diet. Mice can have an epigenetic “mutation” that predisposes them to be obese and have a high risk of disease, despite sharing an identical genome with normal healthy mice. When unhealthy mice with the epigenetic mutation are fed a methyl-rich diet, their offspring are healthy for life.

Reference: www.ncbi.nlm.nih.gov/pmc/articles/PMC2822875/

Resource: http://learn.genetics.utah.edu/content/epigenetics/nutrition/

http://epigenome.eu/en/2,48,872,

www.epibeat.com/tools-technology/dietary-epigenetics-chemoprevention-and-green-tea-cupcakes/523/

 

 

 

 

 

 

Cancer: Epigenetic modifications, such as the silencing of tumor suppression genes or the activation of tumor causing genes (oncogenes) can cause cancer. Additionally, in most cancers there are large scale modifications in the cancer cell epigenome which can play a role in its proliferation. Understanding what causes the epigenetic alterations and reversing them can help researchers prevent and treat cancer.

Link: http://www.the-scientist.com/?articles.view/articleNo/30739/title/Epigenetic-Changes-in-Cancer/

Neuroscience: Changes in epigenetic marks explain how experiences early in life can shape behavior in adulthood and epigenetic factors can regulate the development and function of the nervous system (such as memory formation). In rats it has been demonstrated that pups raised by inattentive mothers are far more sensitive to stress. This is because inattentive mothering causes the genes that regulate the production of glucocorticoid receptors and control the rat’s sensitivity to stress hormones to become methylated, versus unmethylated in pups of attentive mothers. A better understanding of these mechanisms can help researchers identify treatments for memory disorders caused by aging or diseases like schizophrenia, Alzheimer’s, depression, and drug addiction.

References: http://genesdev.cshlp.org/content/16/1/6.long

Resources: http://discovermagazine.com/2013/may/13-grandmas-experiences-leave-epigenetic-mark-on-your-genes

http://www.metahealthuniversity.com/category/brain-relay-diagnostics/

 

 

 

 

 

Agriculture: Epigenetics is an emerging area of research in livestock nutrition, breeding, and crop improvement. RNAi technology and other epigenetic factors have been used in crops to improve the nutrition content and increase stress and disease tolerance. Epigenetics is important in animal breeding because it can help identify the heritability of complex traits and diseases, and predict how environmental factors will affect animal health and performance.

http://journal.frontiersin.org/Journal/10.3389/fgene.2011.00106/full

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