Although, DNA methylation at the promoter regions of genes usually suppresses gene expression, the function of intragenic (within the gene body) or intergenic DNA methylation remains less clear. Either intragenic or intergenic DNA methylation may play an important role in gene expression regulation. The majority of methylated CpG islands are located in intragenic or intergenic regions, whereas less than 3% of CpG islands in the promoter region of genes were methylated.24 Hypermethylation of intragenic regions (or gene bodies) may have at least two roles: (i) intragenic methylation prevents aberrant transcription from intragenic promoters; and (ii) intragenic methylation increases accuracy of splicing. Similarly, hypermethylation of intergenic regions can inhibit random (or nonspecific) gene transcription. To explore the influence of DNA methylation in regulatory, intragenic, or intergenic regions on the risk of AUDs, several studies have investigated AUD-associated DNA methylation alterations in the peripheral blood37–39 or postmortem brains40,41 of AUD subjects using microarray-based approaches.
