Fig. 2

Cis chromatin features regulating PRC2 enzymatic activity or genomic targeting. a Features of PRC2-binding regions. In Drosophila, PREs were identified as DNA elements that recruit PRC2 via interaction with other PcG proteins (i.e., PHO) or TFs. In mammals, both the DNA motif sequence and conformation in CpG islands (CGIs) regulate PRC2 recruitment. b DNA methylation and histone modifications affect PRC2 activity. DNA methylation and PRC2 can be mutually exclusive or can coexist, depending on cell context, suggesting that unknown factors remain to be determined (left). Histone modifications H3K4me3 and H3K36me3 constrain PRC2 activity (middle), while H3K27me3 and H2AK119ub1 stimulate PRC2 catalytic activity or direct its recruitment, respectively (right). c Nascent RNAs regulating PRC2 recruitment depend on transcriptional status. PRC2 interacts promiscuously with multitudinous RNAs. For the repressed genes (left), RNA is transcribed at a very low rate, and the majority of the RNA remains attached to chromatin. Thus, PRC2 bound to the RNA is in very close proximity to the chromatin, allowing PRC2 to slowly deposit H3K27me3 despite low activity. Although binding to RNA antagonizes the allosteric activation of PRC2, these inhibitory effects gradually decrease with the accumulation of H3K27me3, ultimately establishing stable PRC2-mediated gene repression. However, in the active genes that are largely free of PRC2 (right), RNA is transcribed at a very high rate, and most of the RNA is freed from chromatin. Hence, any PRC2 bound to RNA is also consequently removed with inhibited activity, and new RNA can be transcribed continuously, eventually expelling PRC2 from the chromosome