Role of histone H2A ubiquitination in polycomb silencing
Role of histone H2A ubiquitination in polycomb silencing
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DOI：
10.1038/nature02985
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发表时间：
2004-10-14
期刊：
影响因子：
64.8
通讯作者：
Zhang, Y
中科院分区：
文献类型：
--
作者：
Wang, HB;Wang, LJ;Zhang, Y
组蛋白的共价修饰在调节染色质动力学和转录中很重要（1，2）。这种修饰的一个例子是泛素化，它主要发生在组蛋白H2 A和H2 B上（3）。尽管最近的研究已经发现了参与组蛋白H2 B泛素化的酶（4-6）和H2 B泛素化与组蛋白甲基化之间的“串扰”（7，8），但负责H2 A泛素化的酶和功能尚不清楚。在这里，我们报告的E3泛素连接酶复合物，是特定的组蛋白H2 A的纯化和功能特性。该复合物被称为hPRC 1 L（human Polycomb repressive complex 1-like），由几种Polycomb组蛋白组成，包括Ring 1，Ring 2，Bmi 1和HPH 2。hPRC 1 L在赖氨酸119处单泛素化核小体组蛋白H2 A。降低Ring 2的表达导致HeLa细胞中泛素化H2 A水平的显著降低。染色质免疫沉淀分析表明dRing与泛素化H2 A在果蝇Ubx基因的PRE和启动子区在翅成虫盘中共定位。通过RNA干扰去除SL 2组织培养细胞中的dRing导致H2 A泛素化的丧失，伴随着Ubx的去阻遏。因此，我们的研究确定了H2 A泛素连接酶，并将H2 A泛素化与Polycomb沉默联系起来。
Covalent modification of histones is important in regulating chromatin dynamics and transcription(1,2). One example of such modification is ubiquitination, which mainly occurs on histones H2A and H2B(3). Although recent studies have uncovered the enzymes involved in histone H2B ubiquitination(4-6) and a 'cross-talk' between H2B ubiquitination and histone methylation(7,8), the responsible enzymes and the functions of H2A ubiquitination are unknown. Here we report the purification and functional characterization of an E3 ubiquitin ligase complex that is specific for histone H2A. The complex, termed hPRC1L ( human Polycomb repressive complex 1-like), is composed of several Polycomb-group proteins including Ring1, Ring2, Bmi1 and HPH2. hPRC1L monoubiquitinates nucleosomal histone H2A at lysine 119. Reducing the expression of Ring2 results in a dramatic decrease in the level of ubiquitinated H2A in HeLa cells. Chromatin immunoprecipitation analysis demonstrated colocalization of dRing with ubiquitinated H2A at the PRE and promoter regions of the Drosophila Ubx gene in wing imaginal discs. Removal of dRing in SL2 tissue culture cells by RNA interference resulted in loss of H2A ubiquitination concomitant with derepression of Ubx. Thus, our studies identify the H2A ubiquitin ligase, and link H2A ubiquitination to Polycomb silencing.