Format

Send to

Choose Destination
Behav Brain Res. 2015 Jun 1;286:236-240. doi: 10.1016/j.bbr.2015.03.002. Epub 2015 Mar 6.

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

Author information

1
Neuroscience training program, Departments of, University of Wisconsin, Madison, WI, USA.
2
Department of Psychiatry, University of Wisconsin, Madison, WI, USA.
3
Department of Pediatrics, University of Wisconsin, Madison, WI, USA.
4
The Waisman Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
5
Biotechnology Center, University of Wisconsin, Madison, WI, USA.
#
Contributed equally

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.

KEYWORDS:

5-hmC; Acute stress; DNA methylation; Epigenetics

PMID:
25746451
PMCID:
PMC4398338
DOI:
10.1016/j.bbr.2015.03.002
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center