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EtOH contributes to cerebellar pathophysiology. Fragile\u2010X mental retardation protein (<jats:styled-content style=\"fixed-case\">FMRP<\/jats:styled-content>) is a complex regulator of <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> and synaptic plasticity implicated in fragile\u2010X tremor and ataxia syndrome, a phenotype featuring increased <jats:italic>Fmr1 <\/jats:italic><jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression. Recent studies have implicated glutamatergic targets of <jats:styled-content style=\"fixed-case\">FMRP<\/jats:styled-content> in hereditary cerebellar ataxias including the main cerebellar excitatory amino acid (<jats:italic>Eaa1<\/jats:italic>) transporter and a subtype of metabotropic glutamate receptor (<jats:italic>Grm5<\/jats:italic>). However, EtOH\u2010induced changes in cerebellar <jats:italic>Fmr1<\/jats:italic> expression and its epigenetic regulation have not been investigated. Here, we examined the effects of acute EtOH exposure on ataxic behavior, gene expression, and epigenetic regulation of the <jats:italic>Fmr1<\/jats:italic> gene and its glutamatergic targets in the rat cerebellum.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male adult Sprague Dawley rats received acute EtOH (2\u00a0g\/kg) intraperitoneally 1\u00a0hour prior to ataxic behavioral testing on the accelerating rotarod and were sacrificed immediately thereafter. Cerebellar tissues were analyzed for gene expression and epigenetic regulation of the <jats:italic>Fmr1<\/jats:italic> gene and its glutamatergic targets in the rat cerebellum using real\u2010time quantitative polymerase chain reaction (PCR) and chromatin immunoprecipitation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Acute EtOH exposure caused marked ataxia on the accelerating rotarod test compared with saline\u2010treated controls. This ataxic response was associated with increases in <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> levels of <jats:italic>Fmr1<\/jats:italic>,<jats:italic> postsynaptic density 95 (Psd95)<\/jats:italic>,<jats:italic> Eaa1<\/jats:italic>, and <jats:italic>Grm5<\/jats:italic> in the cerebellum. In addition, we found increased H3K27 acetylation both at the promoter region of <jats:italic>Fmr1<\/jats:italic> and at a proposed cyclic adenosine monophosphate (cAMP) response\u2010element binding (<jats:styled-content style=\"fixed-case\">CREB<\/jats:styled-content>) site downstream of the <jats:italic>Fmr1<\/jats:italic> transcription start site. Furthermore, acute EtOH exposure significantly increased <jats:italic>Creb1<\/jats:italic> and the histone acetyltransferases (HAT) <jats:styled-content style=\"fixed-case\">CREB<\/jats:styled-content> binding protein (<jats:italic>Cbp<\/jats:italic>), and <jats:italic>p300 <\/jats:italic><jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> transcripts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Overall, EtOH regulates cerebellar <jats:italic>Fmr1<\/jats:italic> expression most likely via HAT\u2010mediated increase in histone acetylation. We propose that <jats:styled-content style=\"fixed-case\">FMRP<\/jats:styled-content> regulation of glutamatergic transcripts plays an important role in disrupting the excitatory\u2013inhibitory balance in the cerebellum underlying EtOH\u2010induced ataxia.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.14044","type":"journal-article","created":{"date-parts":[[2019,4,10]],"date-time":"2019-04-10T13:16:31Z","timestamp":1554902191000},"page":"1191-1198","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Acute Ethanol Produces Ataxia and Induces <i>Fmr1<\/i> Expression via Histone Modifications in the Rat Cerebellum"],"prefix":"10.1111","volume":"43","author":[{"given":"Russell S.","family":"Dulman","sequence":"first","affiliation":[{"name":"Department of Psychiatry Center for Alcohol Research in Epigenetics University of Illinois at Chicago Chicago Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Auta","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Center for Alcohol Research in Epigenetics University of Illinois at Chicago Chicago Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tara","family":"Teppen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Center for Alcohol Research in Epigenetics University of Illinois at Chicago Chicago Illinois"},{"name":"Jesse Brown Veterans Affairs Medical Center Chicago Illinois"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7139-8464","authenticated-orcid":false,"given":"Subhash C.","family":"Pandey","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Center for Alcohol Research in Epigenetics University of Illinois at Chicago Chicago Illinois"},{"name":"Department of Anatomy and Cell Biology University of Illinois at Chicago  Chicago Illinois"},{"name":"Jesse Brown Veterans Affairs Medical Center Chicago 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