Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription
Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription
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DOI：
10.1016/j.cell.2005.10.023
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发表时间：
2005-11-08
期刊：
影响因子：
64.5
通讯作者：
Workman, JL
中科院分区：
文献类型：
--
作者：
Carrozza, MJ;Li, B;Workman, JL
酵母Rpd3组蛋白去乙酰化酶在基因转录活跃中起重要作用。我们通过MudPIT分析表征了两种不同的Rpd3复合物，Rpd3L和Rpd3S。这两种复合物共享一个三亚基核心，Rpd3L含有与启动子靶向辅阻遏物一致的独特亚基。Rco1和Eaf3是Rpd3S的特异性亚基。RCO 1和EAF 3的突变体在FLO8和STE11开放阅读框（ORF）中表现出乙酰化增加，并在这些ORF的体内出现异常转录物。RNA聚合酶II相关的SET2组蛋白甲基转移酶的突变体也显示出这些缺陷。Set2在Rpd3S的上游起作用，Eaf 3甲基组蛋白结合染色体结构域对于Rpd3S的募集和STE11 ORF内的去乙酰化是重要的。这些数据表明，Pol II相关的Set2甲基化H3，提供转录记忆，其通过Rpd3S发出ORF脱乙酰化的信号。这消除了转录延伸相关的乙酰化，以抑制基因内转录起始。
Yeast Rpd3 histone deacetylase plays an important role at actively transcribed genes. We characterized two distinct Rpd3 complexes, Rpd3L and Rpd3S, by MudPIT analysis. Both complexes shared a three subunit core and Rpd3L contains unique subunits consistent with being a promoter targeted corepressor. Rco1 and Eaf3 were subunits specific to Rpd3S. Mutants of RCO1 and EAF3 exhibited increased acetylation in the FLO8 and STE11 open reading frames (ORFs) and the appearance of aberrant transcripts initiating within the body of these ORFs. Mutants in the RNA polymerase II-associated SET2 histone methyltransferase also displayed these defects. Set2 functioned upstream of Rpd3S and the Eaf3 methyl-histone binding chromodomain was important for recruitment of Rpd3S and for deacetylation within the STE11 ORF. These data indicate that Pol ll-associated Set2 methylates H3 providing a transcriptional memory which signals for deacetylation of ORFs by Rpd3S. This erases transcription elongation-associated acetylation to suppress intragenic transcription initiation.