Methylation of cytosine, usually at CpG dinucleotides, is involved in epigenetic regulation of gene expression. Promoter methylation is typically associated with repression, whereas genic methylation correlates with transcriptional activity42. We used reduced representation bisulfite sequencing (RRBS) to quantitatively profile DNA methylation for an average of 1.2 million CpGs in each of 82 cell lines and tissues (8.6% of non-repetitive genomic CpGs), including CpGs in intergenic regions, proximal promoters, and in intragenic regions (gene bodies)43, although it should be noted that the RRBS method preferentially targets CpG rich islands. We found 96% of CpGs exhibited differential methylation in at least one cell type or tissue assayed (K. Varley et al. Personal Communication), and levels of DNA methylation correlated with chromatin accessibility. The most variably methylated CpGs are found more often in gene bodies and intergenic regions, rather than in promoters and upstream regulatory regions. In addition, we identified an unexpected correspondence between unmethylated genic CpG islands and binding by P300, a histone acetyltransferase linked to enhancer activity44.
