DSIF and RNA polymerase II CTD phosphorylation coordinate the recruitment of Rpd3S to actively transcribed genes.
DSIF and RNA polymerase II CTD phosphorylation coordinate the recruitment of Rpd3S to actively transcribed genes.
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DOI：
10.1371/journal.pgen.1001173
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发表时间：
2010-10-28
期刊：
影响因子：
4.5
通讯作者：
Robert F
中科院分区：
文献类型：
--
作者：
Drouin S;Laramée L;Jacques PÉ;Forest A;Bergeron M;Robert F
组蛋白去乙酰化酶Rpd3是两个不同复合物的一部分：大复合物（Rpd3L）和小复合物（Rpd3S）。Rpd3L针对基因抑制的特定启动子，而Rpd3S则被募集到orf中，在RNA聚合酶II之后使组蛋白去乙酰化，以防止基因内的隐化起始。Set2甲基转移酶对赖氨酸36处组蛋白H3的甲基化被认为介导了Rpd3S的募集。在这里，我们通过ChIP-Chip证实Rpd3S结合了活性orf。然而，令人惊讶的是，Rpd3S并不是被招募到所有的活性基因上，它的招募是与set2无关的。然而，在没有H3K36甲基化的情况下募集的Rpd3S复合物似乎是无活性的。最后，我们提出的证据表明，酵母DSIF复合物（Spt4/5）和Kin28和Ctk1对RNA聚合酶II的磷酸化参与了Rpd3S向活性基因的募集。综上所述，我们的数据支持一个模型，即在Rpd3S募集到RNA聚合酶II c端结构域后，set2依赖性组蛋白H3甲基化是激活Rpd3S所必需的。当基因被转录时，组蛋白n端尾部的乙酰化发生在核小体上，从而帮助RNA聚合酶II通过核小体。然而，组蛋白乙酰化必须在聚合酶之后逆转，以防止转录在错误的地方开始。Rpd3S是一种组蛋白去乙酰化酶复合体，被转录基因招募来完成这一功能。Rpd3S复合体包含一个被认为负责Rpd3S与基因关联的色域，因为它与甲基化组蛋白相互作用，甲基化组蛋白是转录基因上发现的一种特征。在这里，我们表明Rpd3S募集到转录基因不需要组蛋白甲基化。我们发现Rpd3S实际上是通过一种涉及RNA聚合酶II c端结构域磷酸化的机制募集的，这种机制是由一种称为DSIF的转录延伸复合体调节的。我们提出Rpd3S染色体结构域和甲基化组蛋白之间的相互作用有助于在脱乙酰酶被招募到延长RNA聚合酶后将其锚定在其底物上。
Histone deacetylase Rpd3 is part of two distinct complexes: the large (Rpd3L) and small (Rpd3S) complexes. While Rpd3L targets specific promoters for gene repression, Rpd3S is recruited to ORFs to deacetylate histones in the wake of RNA polymerase II, to prevent cryptic initiation within genes. Methylation of histone H3 at lysine 36 by the Set2 methyltransferase is thought to mediate the recruitment of Rpd3S. Here, we confirm by ChIP–Chip that Rpd3S binds active ORFs. Surprisingly, however, Rpd3S is not recruited to all active genes, and its recruitment is Set2-independent. However, Rpd3S complexes recruited in the absence of H3K36 methylation appear to be inactive. Finally, we present evidence implicating the yeast DSIF complex (Spt4/5) and RNA polymerase II phosphorylation by Kin28 and Ctk1 in the recruitment of Rpd3S to active genes. Taken together, our data support a model where Set2-dependent histone H3 methylation is required for the activation of Rpd3S following its recruitment to the RNA polymerase II C-terminal domain. Acetylation of histone N-terminal tails occurs on nucleosomes as a gene is being transcribed, therefore helping the RNA polymerase II traveling through nucleosomes. Histone acetylation, however, has to be reversed in the wake of the polymerase in order to prevent transcription from initiating at the wrong place. Rpd3S is a histone deacetylase complex recruited to transcribed genes to fulfill this function. The Rpd3S complex contains a chromodomain that is thought to be responsible for the association of Rpd3S with genes since it interacts with methylated histones, a feature found on transcribed genes. Here, we show that the recruitment of Rpd3S to transcribed genes does not require histone methylation. We found that Rpd3S is actually recruited by a mechanism implicating the phosphorylation of the RNA polymerase II C-terminal domain and that this mechanism is regulated by a transcriptional elongation complex called DSIF. We propose that the interaction between the Rpd3S chromodomain and methylated histones helps anchoring the deacetylase to its substrate only after it has been recruited to the elongating RNA polymerase.
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影响因子：
64.8
作者：
Gavin, AC;Aloy, P;Superti-Furga, G
通讯作者：
Superti-Furga, G
DOI：
10.1073/pnas.0804424105
发表时间：
2008-06-24
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