Three ways of EZH2 action. (1) The “canonical” action as a transcriptional repressor via methylation of lysine 27 in histone 3 (H3K27); only core components of the PRC2 complex are shown. (2) The transcriptional activation of nonhistone proteins by lysine methylation. (3) The phosphorylation by JAK3 turning EZH2 into a transcriptional activator, described by Yan et al. EED, embryonic ectoderm development; RbAp46/48, retinoblastoma-associated proteins 46/48; SUZ12, suppressor of zeste 12.