Phosphorylation of the PRC2 component Ezh2 is cell cycle-regulated and up-regulates its binding to ncRNA
Phosphorylation of the PRC2 component Ezh2 is cell cycle-regulated and up-regulates its binding to ncRNA
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DOI：
10.1101/gad.1983810
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发表时间：
2010-12-01
影响因子：
10.5
通讯作者：
Reinberg, Danny
中科院分区：
文献类型：
--
作者：
Kaneko, Syuzo;Li, Gang;Reinberg, Danny
当包含多梳抑制复合物2（PRC2）时，Ezh2作为组蛋白H3 Lys 27（H3K27）甲基转移酶起作用。H3K27的三甲基化（H3K27me3）与转录抑制的染色质相关。PRC2靶向特定染色质区域的方式目前尚不清楚，但非编码RNA（ncRNA）已被证明与PRC2相互作用，并可能促进其招募到某些靶基因。在这里，我们表明，Ezh2与HOTAIR和Xist相互作用。Ezh2被细胞周期蛋白依赖性激酶1（CDK1）在苏氨酸残基345和487处以细胞周期依赖性方式磷酸化。残基345处的磷酸模拟物增加了HOTAIR ncRNA与Ezh2的结合，而残基487处的磷酸模拟物无效。发现包含T345的Ezh2结构域对于结合HOTAIR和Xist的59末端是重要的。
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 59 end of Xist.