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 transcriptional silencing (Brenet et al, 2011). Similar to gene-related genomic features, hyper- and hypomethylated DMR-CpGs also showed different distribution patterns with respect to CpGi annotations compared with background (P<2.2 × 10−16, both comparisons; Figure 4a). Specifically, we observed a depletion of DMR-CpGs in CpGi's, with concomitant increases in the other three categories compared with background.
