The Rpd3 core complex is a chromatin stabilization module.
The Rpd3 core complex is a chromatin stabilization module.
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DOI：
10.1016/j.cub.2011.11.042
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发表时间：
2012-01-10
期刊：
影响因子：
9.2
通讯作者：
Carey, Michael
中科院分区：
文献类型：
--
作者：
Chen, Xiao-Fen;Kuryan, Benjamin;Kitada, Tasuku;Tran, Nancy;Li, Jing-Yu;Kurdistani, Siavash;Grunstein, Michael;Li, Bing;Carey, Michael
酿酒酵母Rpd3大(Rpd3L)和小(Rpd3S)组蛋白脱乙酰酶(HDAC)复合体是理解真核生物转录抑制的原型。目前的观点是，它们通过去乙酰化染色质来发挥作用，从而限制了转录机制对潜在DNA的可及性。然而，一项研究表明，当Rpd3催化突变体作为LexA融合蛋白靶向启动子时，仍具有显著的抑制能力。我们用生化方法研究了Rpd3复合体的HDAC不依赖于HDAC的性质，发现了一种伴侣功能，它在体外促进组蛋白沉积到DNA上，以及一种新的活性，它防止核小体驱逐，但不能通过依赖于ATP的RSC复合体介导的重塑。这些不依赖于HDAC的活性在体外抑制核小体模板上的POL II转录。重要的是，内源性Rpd3复合体的功能可以用由Sin3、Rpd3和Ume1组成的重组Rpd3核心复合体来概括，但不能用单个亚基来概括。为了验证Rpd3有助于染色质在体内稳定的假设，我们测量了全基因组的组蛋白H3密度，发现在Rpd3缺失突变体的启动子处它被降低，但在催化突变体中部分恢复。重要的是，对H3密度的影响在RSC丰富的基因上最为明显。我们的数据表明，Rpd3核心复合体可能通过一种新的核小体稳定功能而有助于抑制。
The S. cerevisiae Rpd3 large (Rpd3L) and small (Rpd3S) histone deacetylase (HDAC) complexes are prototypes for understanding transcriptional repression in eukaryotes. The current view is that they function by deacetylating chromatin, thereby limiting accessibility of the transcriptional machinery to the underlying DNA. However, one study showed that an Rpd3 catalytic mutant retains substantial repression capability when targeted to a promoter as a LexA fusion protein. We investigated the HDAC-independent properties of the Rpd3 complexes biochemically and discovered a chaperone function, which promotes histone deposition onto DNA in vitro, and a novel activity, which prevents nucleosome eviction but not remodeling mediated by the ATP-dependent RSC complex. These HDAC-independent activities inhibit Pol II transcription on a nucleosomal template in vitro. Importantly, the functions of the endogenous Rpd3 complexes can be recapitulated with recombinant Rpd3 core complex comprising Sin3, Rpd3 and Ume1, but not with the individual subunits. To test the hypothesis that Rpd3 contributes to chromatin stabilization in vivo, we measured histone H3 density genomewide and found it was reduced at promoters in an Rpd3 deletion mutant but partially restored in a catalytic mutant. Importantly, the effects on H3 density are most apparent on RSC-enriched genes. Our data suggest that the Rpd3 core complex could contribute to repression via a novel nucleosome stabilization function.
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影响因子：
13.8
作者：
Das, Chandrima;Tyler, Jessica K.;Churchill, Mair E. A.
通讯作者：
Churchill, Mair E. A.
DOI：
10.1016/j.bbagrm.2009.05.007
发表时间：
2009-06
期刊：
Biochimica et biophysica acta
影响因子：
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作者：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
3.6
作者：
Ruiz-Roig, Claudia;Vieitez, Cristina;de Nadal, Eulalia
通讯作者：
de Nadal, Eulalia