Methylation at arginine 17 of histone H3 is linked to gene activation

Methylation at arginine 17 of histone H3 is linked to gene activation
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DOI:
10.1093/embo-reports/kvf013
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发表时间:
2002-01-01
期刊:
影响因子:
7.7
通讯作者:
Kouzarides, T
Kouzarides, T
中科院分区:
生物学2区
文献类型:
--
作者:
Bauer, UM;Daujat, S;Kouzarides, T

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在体外,核激素受体共激活剂CARM1具有在精氨酸残基上甲基化组蛋白H3的潜力。在瞬时转染试验中,CARM1的甲基转移酶活性对其共激活因子的功能是必要的。然而,这种甲基转移酶在体内的作用尚不清楚,因为精氨酸的甲基化不容易在组蛋白上检测到。我们提出了一种抗体,可以特异性识别组蛋白H3的甲基化精氨酸17 (R17),这是CARM1甲基化的主要位点。利用这种抗体,我们发现甲基化的R17在体内存在。染色质免疫沉淀分析表明,当雌激素受体调控的pS2基因被激活时,组蛋白H3上的R17甲基化显著上调。与甲基化R17的出现一致,CARM1被发现与pS2基因上的组蛋白相关。综上所述,这些结果表明CARM1被招募到一个活跃的启动子上,并且在这种活跃状态下,CARM1介导的组蛋白H3上的R17甲基化在体内发生。
The nuclear hormone receptor co-activator CARM1 has the potential to methylate histone H3 at arginine residues in vitro. The methyltransferase activity of CARM1 is necessary for its co-activator functions in transient transfection assays. However, the role of this methyltransferase in vivo is unclear, given that methylation of arginines is not easily detectable on histones. We have raised an antibody that specifically recognizes methylated arginine 17 (R17) of histone H3, the major site of methylation by CARM1. Using this antibody we show that methylated R17 exists in vivo. Chromatin immunoprecipitation analysis shows that R17 methylation on histone H3 is dramatically upregulated when the estrogen receptor-regulated pS2 gene is activated. Coincident with the appearance of methylated R17, CARM1 is found associated with the histones on the pS2 gene. Together these results demonstrate that CARM1 is recruited to an active promoter and that CARM1-mediated R17 methylation on histone H3 takes place in vivo during this active state.