Hippocampal increase of 5-hmC in the glucocorticoid receptor gene following acute stress.
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.
Neuroscience training program, Departments of, University of Wisconsin, Madison, WI, USA.|Department of Psychiatry, University of Wisconsin, Madison, WI, USA.
Sisi
S
Li
Department of Psychiatry, University of Wisconsin, Madison, WI, USA.
Ligia A
LA
Papale
Department of Pediatrics, University of Wisconsin, Madison, WI, USA.|The Waisman Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Douglas B
DB
Kintner
Biotechnology Center, University of Wisconsin, Madison, WI, USA.
Grzegorz
G
Sabat
Biotechnology Center, University of Wisconsin, Madison, WI, USA.
Gregory A
GA
Barrett-Wilt
Department of Pediatrics, University of Wisconsin, Madison, WI, USA.|The Waisman Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Pelin
P
Cengiz
Department of Psychiatry, University of Wisconsin, Madison, WI, USA.
Reid S
RS
Alisch
D020413:3' Untranslated Regions; D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000208:Acute Disease; D000818:Animals; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000378:metabolism* / Q000473:pathology
D020413:3' Untranslated Regions; C575863:NR3C1 protein, mouse; D011965:Receptors, Glucocorticoid; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine
5-hmC; Acute stress; DNA methylation; Epigenetics