Overall, MLL/COMPASS and polycomb complexes epigenetically regulate loci susceptible to DNA hypermethylation in cancer cells, and the opposing activities of PRC1 and MLL/COMPASS and PRC2 likely serve to establish and/or maintain a chromatin environment that finely regulates both pro- and anti-DNA methylation recruitment signals at these epigenetically metastable loci. Here, PRC1 is linked to cancer.