Our chromatin immunoprecipitation and genomic sequencing (ChIP-Seq)-based analysis in the postmortem hippocampus of cocaine addicts and alcoholics revealed significant changes in histone H3 lysine 4 trimethylation (H3K4me3) (Zhou et al., 2011), a histone mark known to be associated with activation of gene expression. Similar to the changes observed in gene expression, there was a more widespread and greater impact in response to chronic cocaine exposure than to alcohol exposure. There were also concordant changes between H3K4me3 and gene expression at some loci. In cocaine addicts, these included components of the mitochondrial oxidative phosphorylation pathway or regulators of cellular energy metabolism such as NDUFS2, NDUFA12L, UQCRB, INSR, and IGF1R; genes involved in LTP and other neuronal functions such as calmodulin 2 (CALM2), Synaptophysin-like protein 2 (SYPL2), sodium/chloride-dependent neurotransmitter transporter (SLC6A15), and nociceptin (PNOC). In alcoholics, there were concordant changes between H3K4me3 and gene expression of Protocadherin alpha-7 (PCDHA7), Aquaporin-11 (AQP11), and potassium inwardly-rectifying channel, subfamily J, member 5 (CIR), all of which are involved in critical neuronal and cellular functions. Globally, among all 13,113 histone H3K4me3 peaks mapped to the promoters
