Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing
Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing
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DOI：
10.1016/j.molcel.2005.12.002
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发表时间：
2005-12-22
期刊：
影响因子：
16
通讯作者：
Zhang, Y
中科院分区：
文献类型：
--
作者：
Cao, R;Tsukada, Y;Zhang, Y
Polycomb group（PcG）蛋白存在于至少两种生物化学上不同的蛋白质复合物中，EED-EZH 2复合物和PRC 1复合物，其分别具有H3-K27甲基转移酶和H2 A-K119泛素E3连接酶活性。酶的活性是如何调节的，它们在Hox基因沉默中的作用是什么还不清楚。在这里，我们证明了Bmi-1和Ring 1A，PRC 1复合物的两个组成部分，在H2 A泛素化和Hox基因沉默中发挥重要作用。我们发现，这两种蛋白质积极调节H2 A泛素化。染色质免疫沉淀（ChIP）试验表明，Bmi-1和其他组件的两个PcG复合物结合到HoxC 13的启动子。敲除Bmi-1导致H2 A泛素化的不显著损失和Hoxc 13表达的上调，而EZH 2介导的H3-K27甲基化不受影响。我们的研究结果表明，EZH 2介导的H3-K27甲基化的PRC 1上游的功能，并建立了一个关键的作用Bmi-1和Ring 1A在H2 A泛素化和Hox基因沉默。
Polycomb group (PcG) proteins exist in at least two biochemically distinct protein complexes, the EED-EZH2 complex and the PRC1 complex, that respectively possess H3-K27 methyltransferase and H2A-K119 ubiquitin E3 ligase activities. How the enzymatic activities are regulated and what their role is in Hox gene silencing are not clear. Here, we demonstrate that Bmi-1 and Ring1A, two components of the PRC1 complex, play important roles in H2A ubiquitylation and Hox gene silencing. We show that both proteins positively regulate H2A ubiquitylation. Chromatin immunoprecipitation (ChIP) assays demonstrate that Bmi-1 and other components of the two PcG complexes bind to the promoter of HoxC13. Knockout Bmi-1 results insignificant loss of H2A ubiquitylation and upregulation of Hoxc13 expression, whereas EZH2-mediated H3-K27 methylation is not affected. Our results suggest that EZH2-mediated H3-K27 methylation functions upstream of PRC1 and establishes a critical role for Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing.