It is believed that only 10-20% of our genes are active in any cell. This prevents genes of one cell type from being expressed in another. For example, the gene for eye color only expresses in the eyes, not the liver, skin or brain. The best example of epigenetic changes in eukaryotic biology is the process of cellular differentiation - especially during embryonic development, in which genes use epigenetics to guide proper development of stem cells into different cells of the body. During morphogenesis, totipotent stem cells become the various pluripotent cell lines of the embryo which in turn become fully differentiated cells. In other words, a single fertilized egg cell - the zygote - changes into the many cell types including neurons, muscle cells, epithelium, blood vessels etc. as it continues to divide. It does so by activating some genes while inhibiting others, through epigenetic mechanisms.
In some cases, different DNA methylation effects from the mother and father compete to determine which parent contributes a given genetic or physical trait. This explains why individuals with the same genome, such as identical twins, exhibit different characteristics, depending on whose epigenetic effects - the mother's or the father's - predominated in each infant.
Control of gene expression can be handled in different ways. Sometimes, small molecules - proteins, protein complexes, or small bits of RNA - bind to DNA, changing its ability to give instructions. For example, in times of environmental stress, the body produces molecules to modify DNA and turn on or off genes that help it endure difficult circumstances. In other cases environmental agents present in foods, household chemicals and environmental pollutants can modify the structure of DNA (without changing the underlying, coding sequence) in a process called DNA methylation, turning genes on and off and affecting what gets translated into RNA and proteins.
While most epigenetic changes occur only within the course of one individual organism's lifetime, in recent years it has become apparent - sometimes rather alarmingly - that some epigenetic changes are inherited from one generation to the next, as a consequence of our exposures to environmental agents (pollutants; contaminants; infectious agents; ...), including our diet.
Based on our current understanding, the primary mechanisms affecting epigenetic regulation include:
It also appears that epigenetic effects can affect behavior: one of the most stunning discoveries was a 2004 epigenetics study in Nature Neuroscience (Weaver et al; referenced below) showing that rats who spent more time grooming their young made those offspring braver and more resilient to stress. The infant rats actually changed their behavior due to epigenetic effects when their mother's grooming caused a particular methylation pattern in the babies' brain DNA. These changes occurred in the hippocampus and the resulting baby rats were less anxious and more well-adjusted than rats deprived of maternal affection. Even more exciting was a 2010 study in the Journal of Epidemiology and Community Health (Maselko et al., referenced below) that found a similar correlation in humans. While the brain structures and DNA of the individuals involved have not been studied, maternal affection at 8 months of age was linked to less anxious, better adjusted adults. Researchers are also investigating whether epigenetic influences might be a contributor to mental illnesses, which could lead to new potential treatments.
In summary, some of the effects of and associations with epigenetics include:
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Cancer development - affected by: Alcohol Diet Environmental carcinogens Genetic factors Infectious agents Physical activity Stress Tobacco |
Behavorial / cognitive effects (refer above) Cellular differentiation (refer above) Diabetes, in female offspring of obese fathers Disease: e.g. diabetes (above); Angelman syndrome; Prader-Willi syndrome; Beckwith-Wiedemann syndrome Evolution Reduced male fertility (see my Environmental Health web page) Transgenerational effects (see my Environmental Health web page) |
Marcus Pembrey (referenced below) and colleagues observed in the överkalix study that the paternal (but not maternal) grandsons of Swedish boys who were exposed during preadolescence to famine in the 19th century were less likely to die of cardiovascular disease; if food was plentiful then diabetes mortality in the grandchildren increased, suggesting that this was a transgenerational epigenetic inheritance. The opposite effect was observed for females - the paternal (but not maternal) granddaughters of women who experienced famine while in the womb (and their eggs were being formed) lived shorter lives on average. [This fascinating transgenerational effect is excellently-described in the PBS NOVA episode "Ghost In Your Genes" (and / or search this transcript for "Overkalix").]
For an additional discussion of transgenerational epigenetic effects (e.g. BPA: bisphenyl A - and male fertility), please refer to my Environmental Health web page.
However, the PBS NOVA program uniquely includes discussion of obesity / coat (fur) color in agouti mice due to diet; health differences between identical twins (autism; cancer); nurture / stress (level mother rats' grooming of pups; autism in human sisters); cognitive effects in rats (anxiety); and epigenetic therapy of cancer patients.
Similarly, the BBC Horizon program uniquely includes discussions of transgenerational epigenetic effects associated with: IVF (in vitro fertilization); and stress (children of Holocaust survivors; children of PTSD - post-traumatic stress disorder - mothers following 9-11).