Schematic representation of the action of Ring1A and Ring1B proteins in promoting the maintenance of AML cells derived from MOZ-TIF2, MLL-AF10, PML-RAR, or AML1-ETO fusion proteins. Ring1 proteins associated with PRC1 complexes catalyze the ubiquitylation of lysine K119 of histone H2A (H2AK119-Ubi). This modification, in addition to the H3K27me3, contributes to repression of genes, including GLIS2 and CDKN2A, promoting the self-renewal of leukemia-initiating cells. Because these normally bivalent promoters also contain the activating chromatin modification H3K4me3, inactivation of Ring1 results in derepression of GLIS2, CDKN2A, and other genes, promoting differentiation.