Unraveling the epigenomic and transcriptomic interplay during alcohol-induced anxiolysis.

Autor: Krishnan HR; Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, 60612, USA.; Jesse Brown Veterans Affairs Medical Center, Chicago, IL, 60612, USA., Zhang H; Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, 60612, USA.; Jesse Brown Veterans Affairs Medical Center, Chicago, IL, 60612, USA., Chen Y; Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, 60612, USA., Bohnsack JP; Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, 60612, USA., Shieh AW; Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, 60612, USA.; Department of Psychiatry, SUNY Upstate Medical University, Syracuse, NY, 13210, USA., Kusumo H; Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, 60612, USA.; Jesse Brown Veterans Affairs Medical Center, Chicago, IL, 60612, USA., Drnevich J; High-Performance Biological Computing, Roy J. Carver Biotechnology Center, University of Illinois-Urbana Champaign, Urbana, IL, 61801, USA., Liu C; Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, 60612, USA.; Department of Psychiatry, SUNY Upstate Medical University, Syracuse, NY, 13210, USA., Grayson DR; Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, 60612, USA., Maienschein-Cline M; Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, 60612, USA.; Research Informatics Core, University of Illinois at Chicago, Chicago, IL, 60612, USA., Pandey SC; Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, 60612, USA. scpandey@uic.edu.; Jesse Brown Veterans Affairs Medical Center, Chicago, IL, 60612, USA. scpandey@uic.edu.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2022 Nov; Vol. 27 (11), pp. 4624-4632. Date of Electronic Publication: 2022 Sep 12.
DOI: 10.1038/s41380-022-01732-2
Abstrakt: Positive effects of alcohol drinking such as anxiolysis and euphoria appear to be a crucial factor in the initiation and maintenance of alcohol use disorder (AUD). However, the mechanisms that lead from chromatin reorganization to transcriptomic changes after acute ethanol exposure remain unknown. Here, we used Assay for Transposase-Accessible Chromatin followed by high throughput sequencing (ATAC-seq) and RNA-seq to investigate epigenomic and transcriptomic changes that underlie anxiolytic effects of acute ethanol using an animal model. Analysis of ATAC-seq data revealed an overall open or permissive chromatin state that was associated with transcriptomic changes in the amygdala after acute ethanol exposure. We identified a candidate gene, Hif3a (Hypoxia-inducible factor 3, alpha subunit), that had 'open' chromatin regions (ATAC-seq peaks), associated with significantly increased active epigenetic histone acetylation marks and decreased DNA methylation at these regions. The mRNA levels of Hif3a were increased by acute ethanol exposure, but decreased in the amygdala during withdrawal after chronic ethanol exposure. Knockdown of Hif3a expression in the central nucleus of amygdala attenuated acute ethanol-induced increases in Hif3a mRNA levels and blocked anxiolysis in rats. These data indicate that chromatin accessibility and transcriptomic signatures in the amygdala after acute ethanol exposure underlie anxiolysis and possibly prime the chromatin for the development of AUD.
(© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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