Moreover, C4 CpGs are strongly overrepresented at binding sites of Polycomb repressive complex 2 (PRC2) proteins (Suz12, EZH2, and Jarid2, Supplementary Fig. 3c), which repress gene expression at bivalent promoters and are implicated in cancers and developmental disorders (reviewed in ref. 40). Here, EZH2 is linked to cancer.