Epigenetics: Your Mom Passed On More Than You Know

By: Ravneet Gill

Stress is a common life event with persisting effects on health and behaviour. Recently, it has been established that stress can potentially alter brain plasticity, through long lasting perturbations [1]. Dynamic epigenetic changes are contributed for molecular modifications in the brain, based on an array of stressors. Findings show extreme/less extreme forms of parental trauma/ stress exposure in parents can affect offspring; physically, behaviourally and cognitively [3]. Factors such as prenatal stress, maternal deprivation/ separation, isolation, etc. can have a developmental influence on well-being and health of the unborn child [3]. Through epigenetic mechanisms [1], experiences of stress can induce social problems, reproductive unsuccessfulness, decreased cognitive ability, etc. [2]. Such molecular alterations influence gene expression without causing modifications of the underlying genetic code [2]. The alterations from the impact of stress are typically through DNA methylation and histones [1].

DNA is made of four types of amino acid bases; adenine, cytosine, guanine and thymine. The addition of small chemical groups to the base pairs on DNA aide in the turning on/off of genes. DNA methylation consists of addition of methyl groups on cytosine amino acids adjacent to guanine amino acids, known as CpG sites. CpG islands are regions categorized by high concentrations of CpG sites; these regions basically contain many CG pairs. Methylation occurs via enzymes called DNA methyltransferases [2].  Mainly, increased methylation of CpG islands reduces gene expression, proving to be “silencing”, whereas the opposite increases expression of genes [1].

A second mechanism involves histone proteins, which package DNA into chromatin. DNA is tightly wrapped around proteins called histones. The DNA can be packaged tightly yielding a “transcriptionally silent” complex called, heterochomatin; or can be packaged loosely to remain active, called euchromatin [1]. Notably, an acetyl chemical group can be added to histone proteins, leading to looser interactions between the histones and DNA, resulting in increased gene transcription. On the contrary, histones without acetyl groups, pack tighter to the DNA causing gene suppression [2].

Epigenetic signatures established through a variety of mechanisms (ex. DNA methylation or histone packaging), are highly responsive to environmental factors. Data suggests that responses can occur across generations. This idea is exemplified by the Holocaust offspring studies, where it was first noted that descendants of survivors had different genetic profiles [3]. Specifically, Holocaust survivor offspring with maternal and paternal PTSD exhibited lower methylation on the NR2C1 gene (increased expression) [3]. Furthermore, a positive association is noted in the decreased methylation of NR2C1 of offspring with intimate partner violence, war stress and genocide exposure. It is now evident that experiences across the lifespan can also induce epigenetic variations. In mice studies, chronic stress was positively associated with reductions in expression of BDNF gene, through decreased histone acetylation [2]. However, it is noted that stress-resilient mice did not face these epigenetic changes, displaying that differential susceptibility to stress is possible [2].

In conclusion, current studies provide evidence for effects of epigenetic mechanisms in altering effects of early and late life experiences. This is indicative of the large impact of stress and social experiences on outcomes such as cognitive ability and intergenerational transmission of stress [1].

[1] Hunter, R. G. (2012). Epigenetic effects of stress and corticosteroids in the brain. Frontiers in Cellular Neuroscience, 6. doi:10.3389/fncel.2012.00018

[2] Gudsnuk, K., & Champagne, F. A. (2012). Epigenetic Influence of Stress and the Social Environment. ILAR Journal, 53(3-4), 279-288. doi:10.1093/ilar.53.3-4.279

[3] Bowers, M. E., & Yehuda, R. (2015). Intergenerational Transmission of Stress in Humans. Neuropsychopharmacology, 41(1), 232-244. doi:10.1038/npp.2015.247

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