Figure 5.

Bivalent chromatin protects promoters from de novo DNA methylation. (A) Percentage of genes, within each of the four classes of genes defined in naive mouse ESCs, whose promoters are DNA hypermethylated in EpiLCs (Shirane et al. 2016) are shown. See also Supplemental Fig. S9C,D. (B) Box plots showing changes in promoter H3K4me3/H3K27me3 levels and gene expression (Yang et al. 2019), for each of the four classes of genes shown in A, during ESC to EpiLC differentiation. (FPKM) Fragments per kilobase per million mapped reads; (RPM) reads per million mapped reads. (C,D) Percentage of genes, within each of the four classes of genes defined in human ESCs, whose promoters are aberrantly DNA hypermethylated in human osteosarcoma (U2OS) (Easwaran et al. 2012) (C) or primary human colorectal tumor (Widschwendter et al. 2007) (D). (E) Log₂ odds ratio, with 95% confidence intervals, of promoter de novo DNA methylation during normal development (mouse ESC to EpiLC differentiation; circle), in cancer (human osteosarcoma and colorectal cancer; diamond and square, respectively), and during aging (Rakyan et al. 2010) (X mark) based on their chromatin state in ESCs. (F) Genes bivalently marked in human ESCs were divided into those that are aberrantly DNA hypermethylated in human osteosarcoma (left) and those that are not (right). Box plots show the distribution of H3K4me3 levels at these gene promoters in human osteoblasts (yellow) and osteosarcoma (purple) (Easwaran et al. 2012). All the P-values were calculated using Fisher's exact test (A,C,D) or two-sided Wilcoxon rank-sum test (F,E). See also Supplemental Figure S9.