Arginine methylation of the histone H3 tail impedes effector binding
Arginine methylation of the histone H3 tail impedes effector binding
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DOI：
10.1074/jbc.c700192200
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发表时间：
2008-02-08
影响因子：
4.8
通讯作者：
Bedford, Mark T.
中科院分区：
文献类型：
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作者：
Iberg, Aimee N.;Espejo, Alexsandra;Bedford, Mark T.
组蛋白尾翻译后修饰通过产生或阻断组蛋白代码阅读器的对接位点或通过改变更高级的染色质结构而导致细胞过程的变化。已知H3 K4 me 3标记活性转录的启动子区域。蛋白质以甲基依赖性方式结合H3 K4，并有助于组蛋白重塑酶和转录辅因子的募集。H3 K4 me 3结合剂具有甲基特异性染色质结合结构域，包括植物同源结构域、染色体和tudor结构域。对效应蛋白中存在的植物同源结构域以及WDR 5的WD 40重复序列的结构分析揭示了这些结构域中的残基与H3 R2之间的关键接触。H3 R2和这些结构域类型之间的密切接触导致了这样的假设，即该精氨酸残基的甲基化拮抗效应蛋白与H3的N-末端尾部的结合。在这里，我们表明，H3尾结合效应蛋白确实对H3 R2甲基化敏感，PRMT 6，而不是CARM 1/PRMT 4，是作用于该位点的主要甲基转移酶。我们已经测试了一组选择的H3 K4效应调控基因在PRMT 6敲除细胞中的表达，发现它们的水平发生了改变。因此，PRMT 6甲基化H3 R2并且是N-末端H3尾结合的负调节剂。
Histone tail post-translational modification results in changes in cellular processes, either by generating or blocking docking sites for histone code readers or by altering the higher order chromatin structure. H3K4me3 is known to mark the promoter regions of active transcription. Proteins bind H3K4 in a methyl-dependent manner and aid in the recruitment of histone-remodeling enzymes and transcriptional cofactors. The H3K4me3 binders harbor methyl-specific chromatin binding domains, including plant homeodomain, Chromo, and tudor domains. Structural analysis of the plant homeodomains present in effector proteins, as well as the WD40 repeats of WDR5, reveals critical contacts between residues in these domains and H3R2. The intimate contact between H3R2 and these domain types leads to the hypothesis that methylation of this arginine residue antagonizes the binding of effector proteins to the N-terminal tail of H3. Here we show that H3 tail binding effector proteins are indeed sensitive to H3R2 methylation and that PRMT6, not CARM1/PRMT4, is the primary methyltransferase acting on this site. We have tested the expression of a select group of H3K4 effector-regulated genes in PRMT6 knockdown cells and found that their levels are altered. Thus, PRMT6 methylates H3R2 and is a negative regulator of N-terminal H3 tail binding.