Cancer cells have been shown to promote DNA hyper-methylation in promoter regions of bivalent genes marked by MLL-mediated H3K4me3 and PRC2-mediated H3K27me3, which are known to be activated upon the differentiation of ES cells [18,19], suggesting that PRC2 fine-tunes the level of promoter DNA methylation in normal cells, and that functional impairment of PRC2 may promote DNA hyper-methylation and subsequent methylation-mediated mutations to drive the development of cancer. The gene discussed is KMT2A; the disease is cancer.