We examined alcohol drinking-induced brain Htr3a DNA methylation and gene expression alterations using the drinking-in-the-dark (DID) CD1 mouse model, and reported reduced methylation levels of Htr3a promoter CpGs in the dorsomedial striatum (DMSTR) but elevated expression levels of Htr3a in the DMSTR in alcohol-drinking mice in comparison to water-drinking mice. Moreover, four studies have investigated the relationship between promoter DNA methylation and gene expression of several candidate genes in the peripheral blood (or lymphoblast cell lines derived from blood lymphocytes) of AUD subjects. A negative correlation of promoter DNA methylation levels with gene expression levels was observed in four candidate genes including HERP,60 DNMT-3b,75 SLC6A4,71 and ANP.58 Additionally, Taqi et al.46 observed a positive correlation of the methylation level of a SNP-CpG (rs2235749; C >T) located in the 3′ UTR of the prodynorphin gene (PDYN) with the expressed level of dynorphins in postmortem dorsolateral prefrontal cortex (dl-PFC) of AUD subjects, thus, supporting the notion that gene body methylation can enhance gene transcription. However, we did not observe a clear-cut relationship between DNA methylation and gene expression at the genome-wide level
