Phosphorylation of the PRC2 component Ezh2 is cell cycle-regulated and up-regulates its binding to ncRNA
- Syuzo Kaneko1,2,4,
- Gang Li1,2,4,
- Jinsook Son2,
- Chong-Feng Xu3,
- Raphael Margueron5,
- Thomas A. Neubert3 and
- Danny Reinberg1,2,6
- 1Howard Hughes Medical Institute, New York University School of Medicine, New York, New York 10016, USA;
- 2Department of Biochemistry, New York University School of Medicine, New York, New York 10016, USA;
- 3Department of Pharmacology, Kimmel Center for Biology and Medicine, Skirball Institute, New York University School of Medicine, New York, New York 10016, USA
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↵4 These authors contributed equally to this work.
Abstract
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.
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Footnotes
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↵6 Corresponding author.
E-MAIL reinbd01{at}nyumc.org; FAX (212) 263-9040.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1983810.
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Supplemental material is available at http://www.genesdev.org.
- Received August 18, 2010.
- Accepted October 19, 2010.
- Copyright © 2010 by Cold Spring Harbor Laboratory Press
Freely available online through the Genes & Development Open Access option.