Figure 4. Resolution of Bivalent Chromatin Domains and DNA Methylation of PcG Target Genes.

In stem cells, a large proportion of developmental regulators carry simultaneously both PcG-mediated H3K27me3 and H2AK119ub1 marks and the H3K4me3 modifications associated with repressive and active chromatin states, respectively. While remaining silent, these “bivalent” loci are maintained in a poised state ready for activation, given that a nonprocessive form of RNA polymerase II phosphorylated at serine 5 localizes to these loci (poised RNA Pol II). Following differentiation, these domains are resolved and retain chromatin modifications denoting either completely repressed (loss of H3K4me3) or activated (loss of H3K27me3 and H2AK119ub1) state. Resolution of the “bivalent” domains appears to require the H3K4me3 JARID demethylases (for repression) or the H3K27me3 demethylases (JMJD3/UTX) and MLL complexes (for activation). PRC1 and PRC2 proteins control DNA methylation by directly interacting with DNA methyltransferases (DNMT).