Hippocampal increase of 5-hmC in the glucocorticoid receptor gene following acute stress
Open accessAbstract
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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Acute stress induces accumulation of 5-hmC in the nr3c1 3' UTR in the mouse hippocampus.
“acute stress induces accumulation of 5-hmC in the nr3c1 3’ untranslated region (UTR) in the mouse hippocampus (147).”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [147]
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Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma
Jiang, S., Postovit, L., Cattaneo, A., Binder, E. B., & Aitchison, K. J. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00808 · Cited by 288 · see citing works
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- Authors
- Li, S., Papale, L. A., Kintner, D. B., Sabat, G., Barrett-Wilt, G. A., Cengiz, P., & Alisch, R. S.
- Affiliations
- University of Wisconsin–Madison (US)
- Corresponding author
- Alisch, Reid S.
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2015-06
- Volume
- 286
- Pages
- 236-240
- ISSN
- 0166-4328 (ISSN-L)
- PMC
- PMC4398338
- OpenAlex
- W2054177937
- Cited by
- 29
- References
- 16
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 5 · 2016: 5 · 2015: 2
- FWCI
- 2.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- the University of Wisconsin-Madison department of Psychiatry (RSA)
- the University of Wisconsin Neuroscience (T32-GM007507)
- the Clinical and Translational Science Award program (TR0000427, TR000428)
- NIH/NCATS (UL1TR000427)
- the Waisman Center (PC)
- NIH (HD03352)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- 5-hydroxymethylcytosine, acute stress, hippocampus, glucocorticoid receptor, NR3C1, 3' untranslated region, DNA methylation, epigenetic modifications, restraint stress, stress response
- MeSH terms
- Acute Disease, Animals, Cytosine, Disease Models, Animal, Hippocampus, Neurons, Random Allocation, Receptors, Glucocorticoid, Restraint, Physical, Stress, Psychological, 3' Untranslated Regions, 5-Methylcytosine, Mice
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