Role of histone H3 lysine 27 methylation in polycomb-group silencing
Role of histone H3 lysine 27 methylation in polycomb-group silencing
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DOI：
10.1126/science.1076997
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发表时间：
2002-11-01
期刊：
影响因子：
56.9
通讯作者：
Zhang, Y
中科院分区：
文献类型：
--
作者：
Cao, R;Wang, LJ;Zhang, Y
Polycomb group（PcG）蛋白在维持HOX基因沉默状态中起重要作用。最近的研究表明，组蛋白甲基化与长期基因沉默有关。然而，PcG介导的基因沉默和组蛋白甲基化之间的联系尚未建立。在这里，我们报告了EED-EZH 2复合物的纯化和表征，EED-EZH 2复合物是果蝇ESC-E（Z）复合物的人类对应物。我们证明，该复合物特异性甲基化核小体组蛋白H3在赖氨酸27（H3-K27）。使用染色质免疫沉淀分析，我们表明H3-K27甲基化与超双胸（Ubx）Polycomb反应元件（PRE）上的E（Z）结合共定位，并依赖于E（Z）结合，并且这种甲基化与Ubx抑制相关。H3-K27上的甲基化促进PRC 1复合物的组分Polycomb（PC）与组蛋白H3氨基末端尾的结合。因此，这些研究建立了组蛋白甲基化和PcG介导的基因沉默之间的联系。
Polycomb group (PcG) proteins play important roles in maintaining the silent state of HOX genes. Recent studies have implicated histone methylation in long-term gene silencing. However, a connection between PcG-mediated gene silencing and histone methylation has not been established. Here we report the purification and characterization of an EED-EZH2 complex, the human counterpart of the Drosophila ESC-E(Z) complex. We demonstrate that the complex specifically methylates nucleosomal histone H3 at lysine 27 (H3-K27). Using chromatin immunoprecipitation assays, we show that H3-K27 methylation colocalizes with, and is dependent on, E(Z) binding at an Ultrabithorax (Ubx) Polycomb response element (PRE), and that this methylation correlates with Ubx repression. Methylation on H3-K27 facilitates binding of Polycomb (PC), a component of the PRC1 complex, to histone H3 amino-terminal tail. Thus, these studies establish a link between histone methylation and PcG-mediated gene silencing.