To gain potential insight into functional and mechanistic characteristics of DMRs, we assessed the overlap of DMR-CpGs with various genomic feature annotations from the rn4 genome. A genome-wide map of the DMRs identified in our study is plotted in Figure 3, including the locations of 30 genes associated with DMRs/CpGs exhibiting the largest differences in methylation between THC- and VEH-exposed groups (as per Table 1). The overlap distributions of hyper- and hypomethylated DMR-CpGs were relatively similar with respect to gene-associated annotations; however, each was significantly different from the distribution observed for all tested CpGs (‘All' P<2.2 × 10−16, both comparisons; Figure 4a). Both hyper- and hypomethylated DMR-CpGs were enriched approximately twofold in exonic and intronic regions (gene bodies) compared with background, which likely explains the bias of DMR-CpGs toward higher levels of methylation (Figure 2a)(Jones, 2012). Although we observed a reduction in gene promoter regions compared with the background CpG set (Figure 4a), promoter-associated DMR-CpGs were preferentially located downstream of the TSS compared with background promoter CpGs (Figure 4b); CpGs positioned downstream of the TSS have been shown to cause
