title: DNA modifications in models of alcohol use disorders.
abstract: Chronic alcohol use and abuse result in widespread changes to gene expression, some of which contribute to the development of alcohol-use disorders (AUD). Gene expression is controlled, in part, by a group of regulatory systems often referred to as epigenetic factors, which includes, among other mechanisms, chemical marks made on the histone proteins around which genomic DNA is wound to form chromatin, and on nucleotides of the DNA itself. In particular, alcohol has been shown to perturb the epigenetic machinery, leading to changes in gene expression and cellular functions characteristic of AUD and, ultimately, to altered behavior. DNA modifications in particular are seeing increasing research in the context of alcohol use and abuse. To date, studies of DNA modifications in AUD have primarily looked at global methylation profiles in human brain and blood, gene-specific methylation profiles in animal models, methylation changes associated with prenatal ethanol exposure, and the potential therapeutic abilities of DNA methyltransferase inhibitors. Future studies may be aimed at identifying changes to more recently discovered DNA modifications, utilizing new methods to discriminate methylation profiles between cell types, thus clarifying how alcohol influences the methylomes of cell-type populations and how this may affect downstream processes. These studies and more in-depth probing of DNA methylation will be key to determining whether DNA-level epigenetic regulation plays a causative role in AUD and can thus be targeted for treatment of the disorder.
authors.affiliation: Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, 2500 Speedway, A4800, Austin, TX 78712, USA.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Tulisiak
authors.affiliation: Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, 2500 Speedway, A4800, Austin, TX 78712, USA; The College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, A1900, Austin, TX 78712, USA.
authors.forename: R Adron
authors.initials: RA
authors.lastname: Harris
authors.affiliation: Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, 2500 Speedway, A4800, Austin, TX 78712, USA; The College of Pharmacy, The University of Texas at Austin, 2409 University Avenue, A1900, Austin, TX 78712, USA. Electronic address: ponomarev@utexas.edu.
authors.forename: Igor
authors.initials: I
authors.lastname: Ponomarev
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics* / Q000378:metabolism; D000437:Alcoholism / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D019175:DNA Methylation / Q000187:drug effects; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D044127:Epigenesis, Genetic / Q000187:drug effects; D006801:Humans
chemical_list: D004791:Enzyme Inhibitors; D015254:DNA Modification Methylases
keywords: Alcohol; DNA hydroxymethylation; DNA methylation; DNMT; Epigenetics; TET