Chapter 13 - Global Functions of PRC2 Complexes

Abstract

The PRC2 complex is well known or producing H3K27me3, associated with silenced Polycomb target genes. However, the predominant activity of PRC2 produces H3K27me2 in an untargeted, genome-wide, hit-and-run mode that methylates 60–70% of all histone H3. The level of H3K27me2 is correlated with low or absent transcriptional activity. Inactivation of PRC2 leads to loss of H3K27me2, global increase in H3K27ac and H3K4me1, and transcriptional activation. Transcriptional activity increases in proportion to the previous levels of H3K27me2 but even highly transcribed genes increase two- to fourfold. These effects indicate that PRC2 is a very dynamic, untargeted modifier of genomic chromatin that operates in constant antagonism with H3K27 acetylation and H3K4 monomethylation. This chapter reviews the evidence for a chromatin surveillance mechanism that restricts access to genomic DNA while allowing transient access to DNA binding proteins and the possibility of stable opening of gene regulatory regions. Functional and evolutionary relationships to PRC1 activities are examined.