PRC2 组件 Ezh2 的磷酸化受细胞周期调控，并上调其与 ncRNA 的结合。
Phosphorylation of the PRC2 component Ezh2 is cell cycle-regulated and up-regulates its binding to ncRNA.
机构信息
Howard Hughes Medical Institute, New York University School of Medicine, New York, 10016, USA.
出版信息
Genes Dev. 2010 Dec 1;24(23):2615-20. doi: 10.1101/gad.1983810.
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.
Ezh2 作为 Polycomb-Repressive Complex 2 (PRC2) 的一部分时，充当组蛋白 H3 赖氨酸 27（H3K27）甲基转移酶。H3K27 的三甲基化（H3K27me3）与转录抑制的染色质相关。目前尚不清楚 PRC2 靶向特定染色质区域的方式，但已表明非编码 RNA（ncRNA）与 PRC2 相互作用，并可能有助于其招募到一些靶基因。在这里，我们表明 Ezh2 与 HOTAIR 和 Xist 相互作用。Ezh2 被细胞周期依赖性激酶 1（CDK1）在苏氨酸残基 345 和 487 处磷酸化。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。包含 T345 的 Ezh2 结构域被发现对于与 HOTAIR 和 Xist 的 5'端结合很重要。
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