Fig. 5: Cell-type-specific hypermethylated regions are enriched for CpG islands, Polycomb targets and CTCF and REST/NSRF.

a, Thirty-eight per cent of the top cell type-specific hypermethylated markers (1,363 of 3,613, binomial P < 1 × 10^–100) overap CpG islands. By comparison, 1.6% of cell-type-specific hypomethylated regions (189 of 11,714) overlap CpG islands, comprising less than 0.9% of the genome (black line). b, These regions are typically enriched for H3K27me3 in other cell types. Shown are average H3K27me3 signals in monocytes and macrophages near all cell-type-specific hypermethylated regions (blue) or near monocyte/macrophage-specific hypermethylated regions (mono; green). c, Similar plots for Polycomb annotations in monocytes and macrophages (chromHMM), for all or monocyte/macrophage-specific markers. d, Motif analysis of cell-type-specific hypermethylated regions (top 100 per cell type) identifies known CTCF and REST/NSRF motifs. HOMER binomial P values are shown. e, Analysis of ChIP–seq data for one such site (chr. 1: 209364093–209364250, highlighted in blue, hg19), specifically methylated in the small intestine and colon epithelium (red box 1) and unmethylated elsewhere. As shown below, this site is bound in multiple cell types and tissues but is mostly unbound in stomach and colon epithelium in vivo (red box 2). f, REST/NSRF motif is present within 14% of the top 100 cell type-specific hypermethylated regions in the endocrine pancreas, 7% of top delta cell markers and 2% of top alpha cell markers, compared with approximately 0.1% in background sequences, in accordance with REST target expression in the endocrine pancreas. HOMER binomial P values are shown. Alv., alveolar; bronch., bronchial; Endo. panc., endocrine pancreas; Ep., epithelium; Oesoph., oesophagus; Oligo, oligodendrocytes; Panc., pancreas; Ute., uterus.