Set9, a novel histone H3 methyltransferase that facilitates transcription by precluding histone tail modifications required for heterochromatin formation
Set9, a novel histone H3 methyltransferase that facilitates transcription by precluding histone tail modifications required for heterochromatin formation
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DOI：
10.1101/gad.967202
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发表时间：
2002-02-15
影响因子：
10.5
通讯作者：
Reinberg, D
中科院分区：
文献类型：
--
作者：
Nishioka, K;Chuikov, S;Reinberg, D
从人类细胞中分离出一种新的组蛋白甲基转移酶，称为Set 9。Set 9包含SET域，但缺乏SET前域和SET后域。Set 9特异性甲基化组蛋白H3（H3-K4）的赖氨酸4（K4）并增强转录激活。组蛋白H3尾部与组蛋白脱乙酰酶NuRD复合物特异性相互作用。Set 9对组蛋白H3-K4的甲基化排除了NuRD与H3尾的结合。此外，H3-K4的甲基化损害Suv 39 h1介导的H3的K9（H3-K9）处的甲基化。Set 9和Suv 39 h1组蛋白甲基转移酶之间的相互作用是特异性的，因为组蛋白甲基转移酶G9 a对H3-K9的甲基化不受H3-K4的Set 9甲基化的影响。我们的研究表明，Set 9介导的H3-K4甲基化通过与组蛋白去乙酰化酶竞争和通过Suv 39 h1阻止H3-K9甲基化而在转录激活中起作用。我们的研究结果表明，组蛋白尾部的甲基化可以对转录产生不同的影响，这取决于其染色体位置，翻译后修饰的组合，以及参与特定修饰的酶（或蛋白质复合物）。
A novel histone methyltransferase, termed Set9, was isolated from human cells. Set9 contains a SET domain, but lacks the pre- and post-SET domains. Set9 methylates specifically lysine 4 (K4) of histone H3 (H3-K4) and potentiates transcription activation. The histone H3 tail interacts specifically with the histone deacetylase NuRD complex. Methylation of histone H3-K4 by Set9 precludes the association of NuRD with the H3 tail. Moreover, methylation of H3-K4 impairs Suv39h1-mediated methylation at K9 of H3 (H3-K9). The interplay between the Set9 and Suv39h1 histone methyltransferases is specific, as the methylation of H3-K9 by the histone methyltransferase G9a was not affected by Set9 methylation of H3-K4. Our studies suggest that Set9-mediated methylation of H3-K4 functions in transcription activation by competing with histone deacetylases and by precluding H3-K9 methylation by Suv39h1. Our results suggest that the methylation of histone tails can have distinct effects on transcription, depending on its chromosomal location, the combination of posttranslational modifications, and the enzyme (or protein complex) involved in the particular modification.