Monoubiquitination of human histone H2B:: The factors involved and their roles in HOX gene regulation
Monoubiquitination of human histone H2B:: The factors involved and their roles in HOX gene regulation
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DOI：
10.1016/j.molcel.2005.09.025
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发表时间：
2005-11-23
期刊：
影响因子：
16
通讯作者：
Reinberg, D
中科院分区：
文献类型：
--
作者：
Zhu, B;Zheng, Y;Reinberg, D
在酵母中，组蛋白H2 B单泛素化是调节组蛋白H3在赖氨酸4和79处甲基化的共转录事件。然而，哺乳动物H2 B单泛素化仍然知之甚少。我们报道，在人类中，600 kDa RNF 20/40复合物是E3连接酶，UbcH 6是用于H2 B-Lysl 20单泛素化的泛素E2缀合酶。RNF 20和RNF 40都是Brel的同源物，Brel是酵母中的E3连接酶。UbcH 6与RNF 20/40和hPAF复合物物理相互作用。与hPAF形成的三聚体复合物在体外刺激H2 B单泛素化活性。因此，UbcH 6、RNF 20/40和hPAF复合物在体内被募集到转录活性基因。RNF 20过表达导致H2 B单泛素化水平升高，随后H3赖氨酸4和79的甲基化水平升高，并刺激HOX基因表达。相反，针对RNF 20/40复合物或hPAF复合物的RNAi减少H2 B单泛素化，降低H3赖氨酸4和79的甲基化水平，并抑制HOX基因表达。
In yeast, histone H2B monoubiquitination is a cotranscriptional event regulating histone H3 methylation at lysines 4 and 79. However, mammalian H2B monoubiquitination remains poorly understood. We report that in humans, the 600 kDa RNF20/40 complex is the E3 ligase and UbcH6 is the ubiquitin E2-conjugating enzyme for H2B-Lysl 20 monoubiquitination. RNF20 and RNF40 are both homologs of Brel, the E3 ligase in the yeast case. UbcH6 physically interacts with RNF20/40 and with the hPAF complex. Formation of a trimeric complex with hPAF stimulates H2B monoubiquitination activity in vitro. Accordingly, UbcH6, RNF20/40, and the hPAF complex are recruited to transcriptionally active genes in vivo. RNF20 overexpression leads to elevated H2B monoubiquitination, subsequently higher levels of methylation at H3 lysines 4 and 79, and stimulation of HOX gene expression. In contrast, RNAi against the RNF20/40 complex or hPAF complex reduces H2B monoubiquitination, lowers methylation levels at H3 lysines 4 and 79, and represses HOX gene expression.