Fig. 6.

A simplified model of gene activation by EZH2. Gene repression and activation by EZH2 are illustrated on the left. EZH2 is recruited to chromatin together with other core subunits, EED, SUZ12, and RBBP4, at least in part by accessory subunits (AS) to mediate H3K27me3 in the context of PRC2. EZH2 can also be recruited to active chromatin independent of PRC2 through unknown mechanisms, where it interacts with components of active transcription machineries, such as the transcriptional coactivator p300. On the right EZH2 phosphorylation by AKT and JAK3 in cancer cells triggers structural transitions of the EZH2 TAD (helices H0, H1, H2, and H3), unlocking the otherwise sequestered gene activation activity. The core fragment of the EZH2 TAD becomes accessible to transcription factors and transcriptional coactivators.