title: Nucleosome-binding activities within JARID2 and EZH1 regulate the function of PRC2 on chromatin.
abstract: Polycomb-repressive complex 2 (PRC2) comprises specific members of the Polycomb group of epigenetic modulators. PRC2 catalyzes methylation of histone H3 at Lys 27 (H3K27me3) through its Enhancer of zeste (Ezh) constituent, of which there are two mammalian homologs: Ezh1 and Ezh2. Several ancillary factors, including Jarid2, modulate PRC2 function, with Jarid2 facilitating its recruitment to target genes. Jarid2, like Ezh2, is present in poorly differentiated and actively dividing cells, while Ezh1 associates with PRC2 in all cells, including resting cells. We found that Jarid2 exhibits nucleosome-binding activity that contributes to PRC2 stimulation. Moreover, such nucleosome-binding activity is exhibited by PRC2 comprising Ezh1 (PRC2-Ezh1), in contrast to PRC2-Ezh2. The presence of Ezh1 helps to maintain PRC2 occupancy on its target genes in myoblasts where Jarid2 is not expressed. Our findings allow us to propose a model in which PRC2-Ezh2 is important for the de novo establishment of H3K27me3 in dividing cells, whereas PRC2-Ezh1 is required for its maintenance in resting cells.
authors.affiliation: Howard Hughes Medical Institute, Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016, USA;
authors.forename: Jinsook
authors.initials: J
authors.lastname: Son
authors.forename: Steven S
authors.initials: SS
authors.lastname: Shen
authors.forename: Raphael
authors.initials: R
authors.lastname: Margueron
authors.forename: Danny
authors.initials: D
authors.lastname: Reinberg
mesh_terms: D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D051379:Mice; D032446:Myoblasts / Q000378:metabolism / Q000473:pathology; D041681:NIH 3T3 Cells; D009707:Nucleosomes / Q000378:metabolism*; D063151:Polycomb Repressive Complex 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D002843:Chromatin; D006657:Histones; C093650:Jarid2 protein, mouse; D009707:Nucleosomes; C498408:Ezh1 protein, mouse; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2
keywords: EZH1; EZH2; JARID2; PRC2; Polycomb