Stress and the dynamic genome: Steroids, epigenetics, and the transposome

Abstract

Stress plays a substantial role in shaping behavior and brain function, often with lasting effects. How these lasting effects occur in the context of a fixed postmitotic neuronal genome has been an enduring question for the field. Synaptic plasticity and neurogenesis have provided some of the answers to this question, and more recently epigenetic mechanisms have come to the fore. The exploration of epigenetic mechanisms recently led us to discover that a single acute stress can regulate the expression of retrotransposons in the rat hippocampus via an epigenetic mechanism. We propose that this response may represent a genomic stress response aimed at maintaining genomic and transcriptional stability in vulnerable brain regions such as the hippocampus. This finding and those of other researchers have made clear that retrotransposons and the genomic plasticity they permit play a significant role in brain function during stress and disease. These observations also raise the possibility that the transposome might have adaptive functions at the level of both evolution and the individual organism.

Keywords: brain; genomic stress response; hippocampus; histone marks; retrotransposon.

Fig. 1.

(A) Description of potentially beneficial actions of transposons that are known to occur at the organismal level. The names next to the connecting lines are those of the elements that have been shown to be involved in the relevant function: e.g., the transposon-derived XIST element governs epigenetically mediated X-chromosome inactivation, and an IAP ERV/LTR retrotransposon created the epigenetically imprinted agouti locus. (B) Description of population-level beneficial effects of transposon endosymbiosis, giving known examples in smaller print: e.g., the evolution of both the mammalian immune system and the placenta have been driven to a large extent by transposon-derived genomic elements. (C) Outline of both known and potential interactions between steroids and transposable elements, with more theoretical interactions followed by a question mark. For instance, those organs that show the highest levels of retrotransposon activity, such as the brain and placenta, also seem to be both steroidogenic and steroid-sensitive although the link remains correlative (see Transposons: Controlling Elements After All).