Hippocampal increase of 5-hmC in the glucocorticoid receptor gene following acute stress

Behavioural Brain Research
Sisi LiReid S Alisch

Abstract

5-Hydroxymethylcytosine (5-hmC) is a novel environmentally sensitive DNA modification that is highly enriched in post-mitotic neurons and is associated with active transcription of neuronal genes. Recently, 5-hmC was functionally linked to learning and cognition and these studies revealed an accumulation of 5-hmC in the prefrontal cortex of mice undergoing fear extinction. These studies led us to hypothesize a role for 5-hmC in response to stress. To test this hypothesis, we combined immunohistochemistry, tandem mass spectrometry, and tet-assisted sodium bisulfite sequencing (TAB-seq) analyses on tissue and DNA from the hippocampus of 7-week old male mice exposed to a single 30-min restraint stress. After first identifying that the broad neuronal distribution of 5-hmC is not disrupted by acute stress, we used TAB-seq to find a stress-induced increase of 5-hmC in the 3'UTR of the glucocorticoid receptor gene (Nr3c1). Nr3c1 has a well-defined role in the stress pathway and these data suggest that 5-hmC contributes to these processes. Together, these data indicate that a deeper investigation of stress-related 5-hmC levels may reveal an environmental impact on this newly discovered epigenetic mark in the brain.

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Citations

Apr 13, 2017·Journal of Molecular Endocrinology·B C J DirvenM J A G Henckens
Jan 25, 2017·Journal of Psychopharmacology·Xabier BengoetxeaMaría J Ramírez
Aug 5, 2017·Frontiers in Genetics·Dong-Qiao ShiWei-Cai Yang
Aug 20, 2016·Environmental Epigenetics·Laura M HackNadine Provençal
Feb 6, 2020·Current Environmental Health Reports·Joseph Kochmanski, Alison I Bernstein
Sep 17, 2016·Learning & Memory·Ashley M BlouinCourtney A Miller
Nov 30, 2019·Frontiers in Psychiatry·Shui JiangKatherine J Aitchison

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