Eaf3 chromodomain interaction with methylated H3-K36 links histone deacetylation to Pol II elongation

Eaf3 chromodomain interaction with methylated H3-K36 links histone deacetylation to Pol II elongation
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DOI:
10.1016/j.molcel.2005.11.021
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发表时间:
2005-12-22
期刊:
影响因子:
16
通讯作者:
Struhl, K
Struhl, K
中科院分区:
生物学1区
文献类型:
--
作者:
Joshi, AA;Struhl, K

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Eaf3是NuA4组蛋白乙酰化酶和Rpd3组蛋白去乙酰化酶复合物的一个组成部分,对酿酒酵母组蛋白乙酰化的全局模式很重要。编码区的优先去乙酰化需要Eaf3染色体结构域和H3-K36被Set2甲基化。Eaf3染色体结构域与甲基化的H3-K36肽相互作用,表明这种相互作用导致Rpd3复合物优先结合和编码区3'部分的组蛋白去乙酰化。然而,Eaf3染色体结构域和H3-K36甲基化对启动子的乙酰化没有显著影响,这表明Eaf3可能在NuA4复合体中具有独特的功能。最后,Eaf3以类似于FACT和Spt6的方式抑制mRNA编码区域的内部起始。我们的研究结果将编码区域的优先去乙酰化模式与RNA聚合酶II c端结构域的H3-K36甲基化和磷酸化的潜在模式联系起来,并最终与转录延伸后抑制性染色质结构恢复的机制联系起来。
Eaf3, a component of the NuA4 histone acetylase and Rpd3 histone deacetylase complexes, is important for the global pattern of histone acetylation in Saccharomyces cerevisiae. Preferential deacetylation of coding regions requires the Eaf3 chromodomain and H3-K36 methylation by Set2. The Eaf3 chromodomain interacts with methylated H3-K36 peptides, suggesting that this interaction leads to preferential association and histone deacetylation of the 3' portions of coding regions by the Rpd3 complex. However, the Eaf3 chromodomain and H3-K36 methylation do not significantly affect acetylation at promoters, suggesting that Eaf3 has a distinct function, presumably in the NuA4 complex. Lastly, Eaf3 inhibits internal initiation within mRNA coding regions in a manner similar to FACT and Spt6. Our results link the pattern of preferential deacetylation at coding regions to the underlying patterns of H3-K36 methylation and phosphorylation of the RNA polymerase II C-terminal domain, and ultimately to the mechanism by which repressive chromatin structure is restored after transcriptional elongation.