DNA methylation is one of the best-studied epigenetic mechanisms. It consists of the covalent addition of a methyl group (-CH3) to the carbon 5 of cytosine, usually in DNA regions called “CpG islands” located in gene promoters. The presence of methylation tends to silence gene expression; its absence tends to activate it.
Methylation is established during embryonic development, modified throughout life in response to experiences, and, crucially, a portion of methylation patterns is transmitted through gametes (sperm and eggs) to offspring. This is what opens the door to the documented transgenerational transmission of trauma.
Key studies: Weaver and Meaney (2004, Nature Neuroscience 7:847-854) showed in rats that maternal behavior (licking and grooming offspring) alters the methylation of the glucocorticoid receptor in the hippocampus of offspring, modifying their lifelong stress response. Yehuda et al. (2016, Biological Psychiatry 80:372-380) documented alterations in FKBP5 gene methylation in children of Holocaust survivors.
In the context of the systemic approach, methylation provides the molecular mechanism that explains how intense parental experiences can leave regulatory imprints on children without needing to invoke vague concepts.
Bibliography
- Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation — Rachel Yehuda et al.. Biological Psychiatry, 80(5), 372-380, 2016.
- Epigenetic regulation of the glucocorticoid receptor in response to maternal behavior — Ian Weaver, Michael Meaney et al.. Nature Neuroscience, 7(8), 847-854, 2004.
- Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice — Katharina Gapp, Isabelle Mansuy et al.. Nature Neuroscience, 17(5), 667-669, 2014.
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Related terms
Epigenetics
The study of changes in gene expression that do NOT alter the DNA sequence, are heritable, and can be activated by life experiences—including trauma.
See entryFKBP5 (stress gene)
A gene that regulates the sensitivity of the glucocorticoid receptor to cortisol. Its epigenetic modifications are one of the central findings in the transgenerational transmission of trauma.
See entryYehuda's studies on Holocaust survivors
Rachel Yehuda's research program at Mount Sinai that documented epigenetic, hormonal, and HPA axis alterations in Holocaust survivors and their descendants.
View detailsMansuy Model (transgenerational transmission in mice)
Studies by Isabelle Mansuy at ETH Zurich that documented, in mice, transmission up to the 4th generation of behavioral effects from early trauma via sperm RNA.
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