divergence of methylation was at lower CpG levels, and the methylation levels were reduced to the genome-wide median level as the CpG content increased (Fig. 2C). Most of the hypermethylated promoters in HCP have a lower CpG content, an observation consistent with the fact that CpG dinucleotides are reduced in vertebrate genomic DNA due to deamination and elimination of mutations during evolution.57 Overall, our results demonstrate that (a) promoter methylation density is related to CpG island density; (b) methylation density has a stronger influence on gene expression than CpG island density; and (c) in ICP and HCP, methylation favors transcriptional repression.
