Cao Ru, Wang Liangjun, Wang Hengbin, Xia Li, Erdjument-Bromage Hediye, Tempst Paul, Jones Richard S, Zhang Yi
Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA.
Science. 2002 Nov 1;298(5595):1039-43. doi: 10.1126/science.1076997. Epub 2002 Sep 26.
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.
多梳蛋白家族（PcG）在维持HOX基因的沉默状态中发挥着重要作用。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介导的基因沉默与组蛋白甲基化之间的联系尚未建立。在此，我们报道了EED-EZH2复合物的纯化和特性，它是果蝇ESC-E(Z)复合物在人类中的对应物。我们证明该复合物特异性地使核小体组蛋白H3的赖氨酸27（H3-K27）发生甲基化。通过染色质免疫沉淀分析，我们发现H3-K27甲基化与E(Z)在超双胸（Ubx）多梳应答元件（PRE）上的结合共定位，并且依赖于这种结合，而且这种甲基化与Ubx的抑制相关。H3-K27上的甲基化促进了PRC1复合物的一个组分多梳蛋白（PC）与组蛋白H3氨基末端尾巴的结合。因此，这些研究建立了组蛋白甲基化与PcG介导的基因沉默之间的联系。
