Chunk #17 — 3. Biological co-expression networks: Transcriptional regulation in alcohol use disorder — 3.1: Epigenetic modifications in the human alcoholic brain
2012). In addition, alcohol-induced up-regulation of genes in GC-rich modules is hypothesized to be associated with increased levels of H3K4 trimethylation (H3K4me3) in promoter regions, again suggesting coordinated regulation of chromatin modification complexes. Furthermore, a global down-regulation of DNA methyltransferase (DNMT1) was observed in all three brain regions of alcoholics, indicating a system-wide change in epigenetic regulation of gene expression. The down-regulation of DNMT1 is consistent with literature showing hypomethylation states in alcoholic brain and blood as well as in cancer and neurodegenerative disorders (Clark et al., 2015; Hervouet et al., 2010; Wang et al., 2016; Zhang et al., 2014a). Recent studies have even suggested that alterations in DNA methylation in the prefrontal cortex are associated with (and might result in) increased risk for AUD (Wang et al., 2016).
