We cannot tell at this time whether the differences found in DNA methylation between the former heroin addicts and controls were due to altered methylation at specific CpG sites within the OPRM1 promoter region or to a global increase in DNA methylation, and whether either has a functional role in heroin addiction. The role of global methylation has been hypothesized to repress transcription of repetitive elements (Maksakova et al. 2008). Altered DNA methylation at specific CpG sites has been shown to alter the expression of various genes (e.g. Iguchi-Ariga and Schaffner 1989; Zhang et al. 2010). At the level of a single gene, methylation at specific CpG sites may prevent the binding of transcriptional activators (Tate and Bird 1993). Alternatively, methyl-CpG binding domains of transcriptional repressors may bind methylated CpG sites to either block the interaction of transcriptional activators with DNA (Tate and Bird 1993) or through the recruitment of histone modifying enzymes, such as histone deacetylases, that may alter surrounding chromatin (Ballestar and Wolffe 2001). In addition, DNA methylation can increase the compaction and rigidity of the nucleosome, which may further repress transcription (Choy et al. 2010).
