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Histone acetylation is an epigenetic mechanism that changes the chromatin architecture, influencing gene transcription, which may further impact neuronal signaling, cognition, and addiction-related behaviors. In this review, we summarize the existing literature on how alcohol exposure impacts histone acetylation and the expression and activity of histone acetyltransferases (HATs) and histone deacetylases (HDACs). Overall, alcohol appears to dynamically regulate histone acetylation and the expression and activity of HATs and HDACs in a brain region-, alcohol quantity-, exposure paradigm-, and sex-specific manner. While general patterns exist, more work is needed to elucidate the precise mechanisms through which alcohol changes histone marks across a variety of experimental and biological conditions, thus changing downstream gene expression. We suggest here that a more nuanced understanding of the relationship between histone acetylation and alcohol consumption is needed. Going forward, unbiased molecular techniques for profiling histone marks across the genome will allow for greater precision in determining the impact of alcohol on epigenetic regulation of transcription. However, these approaches must be performed with consideration to differences in mode and quantity of alcohol exposure, as well as withdrawal time and sex, in order for this research to uncover therapeutic targets for future treatment options. Overall, comprehensive, unbiased studies may yield novel insights into the regulatory role of alcohol-induced epigenetic modifications in the pathophysiology and neuropsychiatric correlates of AUD.<\/jats:p>","DOI":"10.3390\/genes17060637","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:17:31Z","timestamp":1780467451000},"page":"637","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Regulation of Chromatin Acetylation by Alcohol: Dependence on Sex, Brain Region, and Mode of Exposure"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3847-9048","authenticated-orcid":false,"given":"Kelly M.","family":"Abshire","sequence":"first","affiliation":[{"name":"Department of Behavioral Neuroscience, Oregon Health & Science University, 3181 S.W. Sam Jackson Park Rd., Mail Code: L470, Portland, OR 97239, USA"},{"name":"School of Medicine, Oregon Health and Science University, 3181 S.W. Sam Jackson Park Rd., Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4662-3775","authenticated-orcid":false,"given":"Andrey E.","family":"Ryabinin","sequence":"additional","affiliation":[{"name":"Department of Behavioral Neuroscience, Oregon Health & Science University, 3181 S.W. Sam Jackson Park Rd., Mail Code: L470, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deena M.","family":"Walker","sequence":"additional","affiliation":[{"name":"Department of Behavioral Neuroscience, Oregon Health & Science University, 3181 S.W. 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