Phosphorylation of the PRC2 component Ezh2 is cell cycle-regulated and up-regulates its binding to ncRNA.
Ezh2 functions as a histone H3 Lys 27 (H3K27) methyltransferase when comprising the Polycomb-Repressive Complex 2 (PRC2). Trimethylation of H3K27 (H3K27me3) correlates with transcriptionally repressed chromatin. The means by which PRC2 targets specific chromatin regions is currently unclear, but noncoding RNAs (ncRNAs) have been shown to interact with PRC2 and may facilitate its recruitment to some target genes. Here we show that Ezh2 interacts with HOTAIR and Xist. Ezh2 is phosphorylated by cyclin-dependent kinase 1 (CDK1) at threonine residues 345 and 487 in a cell cycle-dependent manner. A phospho-mimic at residue 345 increased HOTAIR ncRNA binding to Ezh2, while the phospho-mimic at residue 487 was ineffectual. An Ezh2 domain comprising T345 was found to be important for binding to HOTAIR and the 5' end of Xist.
Howard Hughes Medical Institute, New York University School of Medicine, New York, 10016, USA.
Syuzo
S
Kaneko
Gang
G
Li
Jinsook
J
Son
Chong-Feng
CF
Xu
Raphael
R
Margueron
Thomas A
TA
Neubert
Danny
D
Reinberg
D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology*; D000071221:Enhancer of Zeste Homolog 2 Protein; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D063151:Polycomb Repressive Complex 2; D063146:Polycomb-Group Proteins; D011485:Protein Binding; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D015854:Up-Regulation
D063146:Polycomb-Group Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D012097:Repressor Proteins; C077885:XIST non-coding RNA; D000071221:Enhancer of Zeste Homolog 2 Protein; C498410:Ezh2 protein, mouse; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2; D016203:CDC2 Protein Kinase