Figure 3.

Genome-wide analysis of DNA methylation in Tet2^m/m and Tet2^−/− ESCs reveals hypermethylation of gene regulatory elements

(A) Genome-wide percent CpG, CHG and CHH methylation levels in Tet2^+/+, Tet2^m/m, and Tet2^−/− ESCs measured by whole-genome bisulfite sequencing (WGBS).

(B) Quantification of differentially methylated regions (DMRs = >5 CpGs, methylation difference >20%, and FDR <0.05) in Tet2^m/m and Tet2^−/− ESCs compared to wildtype ESCs. Note that the majority of DMRs are hypermethylated in both cell types.

(C) Assignment of hypermethylated (hyper-) DMRs in Tet2^m/m and Tet2^−/− ESCs to genomic regions. Note that the majority of DMRs are at promoters and active or primed enhancers.

(D) Profile plots of DNA methylation levels at hyper-DMRs located at promoters and enhancers in Tet2^m/m and Tet2^−/− ESCs.

(E) Percent of DEGs in Tet2^m/m and Tet2^−/− ESCs that overlap with hyper-DMR-associated genes. Note the significant association between downregulated genes and hypermethylated promoters, active and primed enhancers (∗p < 0.05 by hypergeometric test).