Chunk #18 — 3. Biological co-expression networks: Transcriptional regulation in alcohol use disorder — 3.1: Epigenetic modifications in the human alcoholic brain
System-wide epigenetic modifications have also been observed in the hippocampus of human alcoholics and chronic cocaine users (Farris et al., 2015a; Zhou et al., 2011). Chronic alcohol or cocaine exposure altered the expression of genes that are responsible for the regulation of transcription, gene silencing, and chromatin modifications (Zhou et al., 2011). In alcoholic cases, there were H3K4me3 signal changes at the promoters of > 700 expressed genes (uncorrected P < 0.05); however, there was not a significant correlation or individual locus overlap between H3K4me3 and gene expression changes, suggesting that alcohol exposure has only a modest effect on histone H3K4me3 in the hippocampus of human alcoholics. A recent study expanded upon the role of chromatin modifications in regulating gene expression by comparing gene modules constructed from ChIP-seq and RNA-seq datasets obtained from the hippocampus of human alcoholics and chronic cocaine users (Farris et al., 2015a). In contrast to the modest effects observed previously (Zhou et al., 2011), Farris and colleagues observed 35 significant overlaps between the two datasets with 83% of modules having a significant positive correlation between H3K4me3
