Advances in DNA, histone, and RNA methylation mechanisms in the pathophysiology of alcohol use disorder

Alcohol use disorder (AUD) has a complex, multifactorial etiology involving dysregulation across several brain regions and peripheral organs. Acute and chronic alcohol consumption cause epigenetic modifications in these systems, which underlie changes in gene expression and subsequently, the emergence of pathophysiological phenotypes associated with AUD. One such epigenetic mechanism is methylation, which can occur on DNA, histones, and RNA. Methylation relies on one carbon metabolism to generate methyl groups, which can then be transferred to acceptor substrates. While DNA methylation of particular genes generally represses transcription, methylation of histones and RNA can have bidirectional effects on gene expression. This review summarizes one carbon metabolism and the mechanisms behind methylation of DNA, histones, and RNA. We discuss the field’s findings regarding alcohol’s global and gene-specific effects on methylation in the brain and liver and the resulting phenotypes characteristic of AUD.