Furthermore, to understand DNA methylation patterns in genomic regions with different CpG densities, promoters were classified into three categories, adopting similar criteria as used in mouse embryonic stem cells.53 Classification was performed according to the CpG content of the promoter within extended regulatory regions of 1,300 bp upstream and 500 bp downstream of the transcription start site; it is recently understood that the effect of CpG methylation is likely to extend beyond the core of promoter regions54,55 and core promoter regions from 500 bp upstream and 200 bp downstream of the transcription start site were also analyzed. High-density CpG promoters (HCP), containing at least one 500-bp region with GC content ≥0.55 and CpG observed to the expected ratio ≥0.6; low-density CpG promoters (LCP), containing no 500-bp interval with CpG observed to the expected ratio ≥0.4; and intermediate-density CpG promoters (ICP) that lie in between HCP and LCP, and are neither HCPs nor LCPs (Fig. 1A). A summarized methylation level was calculated for each gene based on the average signal intensity of all the probes within the gene’s regulatory region, from
