Search for a general epigenetic mechanism of adaptation
In response to sustained environmental challenges, individuals undergo behavioral adaptation. Epigenetic-based mechanisms, including local DNA methylation and histone secondary modifications, are well suited to explain brain and behavioral adaptation. Indeed, sustained environmental changes such as early adversity and chronic stress can modulate the neuronal epigenome of the exposed individual and its descendants. However, to establish causality between environment, epigenetic changes and behavioral outcome, it must be demonstrated that the epigenome is able to “sense” and “register” sustained environmental effects, store the experience for a long period of time or even permanently, and finally alter neuronal physiology and behavior.
Our laboratory has recently identified a large number of small genomic regions in neurons that, by switching their epigenetic state, respond to sustained (but not short duration) environmental changes. Once switched, the epigenetic state persists and can be even permanent. Switches are embedded in genes and have enhancer activity. Different environmental challenges result in switching in different sets of regions and genes. Finally, environment-induced epigenetic switching is not limited to neurons and found in somatic tissue. These findings provide a foundation for a general epigenetic theory of adaptation. Aspects of this theory, including how epigenetic switches retain experience and elicit neuronal and behavioral responses, are under intense investigation in our laboratory. A similar work in non-neuronal tissues investigates how epigenetic switching underlies adaptation in the liver to lifestyle and dietary changes.
Oh JE, Chambwe N, Klein S, Gal J, Andrews S, Gleason G et al. Differential gene body methylation and reduced expression of cell adhesion and neurotransmitter receptor genes in adverse maternal environment. Translational psychiatry 2013; 3: e218. 22 January 2013.
Sharma A, Klein SS, Barboza L, Lohdi N, Toth M. Principles Governing DNA Methylation during Neuronal Lineage and Subtype Specification. The Journal of Neuroscience 36(5):1711-22, 2016. PMID: 26843651 PMCID: PMC4737779.
Mitchell E, Klein S, Argyropoulos VK, Sharma S, Chan RB, Toth JG, Barboza L, Bavley C, Bortolozzi A, Chen Q, Liu B, Ingenito J, Mark W, Dudakov J, Gross S, Di Paolo G, Artigas F, Brink M, Toth M. Behavioral traits propagate across generations via segregated iterative-somatic and gametic epigenetic mechanisms. Nature Communications 7:11492. DOI: 10.1038/ncomms11492, 2016.