H3K36me3 key to Polycomb-mediated gene silencing in lineage specification

Abstract

A newly uncovered activity of a family of Polycomb-group proteins provides insight into the mechanisms by which active genes become repressed during the transition from pluripotency to restricted cell fates as stem cells undergo lineage specification.

Figure 1

H3K36me3 binding by PHF19 leads to recruitment of PRC2 and de novo gene silencing. (a) The Tudor domain of PHF19 binds H3K36me3 and recruits PRC2 and H3K36me3 demethylases NO66 and KDM2b (also known as Fbxl10). H3K36me3 inhibits the catalytic activity of PRC2. Following demethylation of H3K36, PRC2 is able to trimethylate H3K27. (b) Recruitment of both H3K4me3 demethylase KDM5a (also known as Rbp2 and Jarid1a) and H3K36me3 demethylases NO66 and/or KDM2b leads to removal of histone modifications near the promoter and downstream regions of active genes. This is followed by H3K27 trimethylation by PRC2 and establishment of transcriptional silencing.