期刊
BEHAVIOURAL BRAIN RESEARCH
卷 286, 期 -, 页码 236-240出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbr.2015.03.002
关键词
Acute stress; Epigenetics; DNA methylation; 5-hmC
资金
- University of Wisconsin-Madison department of Psychiatry (RSA)
- University of Wisconsin Neuroscience training grant [T32-GM007507]
- Clinical and Translational Science Award program of NCATS [UL1 TR0000427, KL2 TR000428]
- NIH/NCATS [UL1TR000427]
- Waisman Center
- NIH [P30 HD03352]
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. (C) 2015 Elsevier B.V. All rights reserved.
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