Chunk #16 — 3. Biological co-expression networks: Transcriptional regulation in alcohol use disorder — 3.1: Epigenetic modifications in the human alcoholic brain
Bleich and Hillemacher (2009) initially demonstrated that alcohol alters DNA methylation and expression of individual genes. The first integrative view of transcriptome alterations in human alcoholic brain was performed in the superior frontal cortex, basolateral amygdala, and central amygdala using a microarray platform and WGNCA (Ponomarev et al., 2012). This study identified an unprecedented role for epigenetic regulation in alcoholics. Most genes from GC-rich modules were up-regulated in alcohol abusers, while genes from GC-poor modules were mainly down-regulated. The importance of the genomic GC content in regulating gene expression is well established because many transcription factors and other parts of chromatin modification complexes preferentially bind to GC- or AT-rich motifs (Dekker, 2007; Zhang et al., 2004). Up-regulation of GC-rich modules suggests a critical role of chromatin modifications in the modulation of gene expression in the alcoholic brain (Ponomarev et al., 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
