SUPT3H-less SAGA coactivator can assemble and function without significantly perturbing RNA polymerase II transcription in mammalian cells.
SUPT3H-less SAGA coactivator can assemble and function without significantly perturbing RNA polymerase II transcription in mammalian cells.
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DOI：
10.1093/nar/gkac637
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发表时间：
2022-08-12
影响因子：
14.9
通讯作者：
Vincent, Stephane D.
中科院分区：
文献类型：
--
作者：
Fischer, Veronique;Hisler, Vincent;Scheer, Elisabeth;Lata, Elisabeth;Morlet, Bastien;Plassard, Damien;Helmlinger, Dominique;Devys, Didier;Tora, Laszlo;Vincent, Stephane D.
辅激活因子复合物调节染色质可及性和转录。佐贺（Spt-Ada-Gcn 5 Acetyltransferase）是一种进化上保守的辅激活因子复合物。核心模块支撑整个佐贺复合物并采用组蛋白八聚体样结构，其由形成三个组蛋白折叠（HF）对的六个含组蛋白折叠结构域（HFD）的蛋白组成，其中含双HFD的SUPT 3 H添加一个HF对。Spt 3是SUPT 3 H的酵母直系同源物，与TATA结合蛋白（TBP）在遗传和生物化学上相互作用，并有助于全局RNA聚合酶II（Pol II）转录。在这里，我们证明了（i）从人U2 OS或小鼠胚胎干细胞（mESC）纯化的佐贺可以在没有SUPT 3 H的情况下组装，（ii）SUPT 3 H对于mESC的存活不是必需的，但对于它们的生长和自我更新是必需的，以及（iii）从哺乳动物细胞中缺失SUPT 3 H只影响特定基因亚群的转录。因此，在不存在SUPT 3 H的情况下，未观察到基因启动子处TBP积累的重大变化。因此，SUPT 3 H不是佐贺组装、TBP募集或总体Pol II转录所必需的，但在mESC生长和自我更新中起作用。我们的数据进一步表明，酵母和哺乳动物的佐贺复合物有助于通过不同的机制进行转录调控。在哺乳动物中，佐贺在没有SUPT 3 H的情况下组装，但与酵母不同，SUPT 3 H不需要TBP沉积在启动子上和全局Pol II转录，仅影响基因的子集。
Coactivator complexes regulate chromatin accessibility and transcription. SAGA (Spt-Ada-Gcn5 Acetyltransferase) is an evolutionary conserved coactivator complex. The core module scaffolds the entire SAGA complex and adopts a histone octamer-like structure, which consists of six histone-fold domain (HFD)-containing proteins forming three histone-fold (HF) pairs, to which the double HFD-containing SUPT3H adds one HF pair. Spt3, the yeast ortholog of SUPT3H, interacts genetically and biochemically with the TATA binding protein (TBP) and contributes to global RNA polymerase II (Pol II) transcription. Here we demonstrate that (i) SAGA purified from human U2OS or mouse embryonic stem cells (mESC) can assemble without SUPT3H, (ii) SUPT3H is not essential for mESC survival, but required for their growth and self-renewal, and (iii) the loss of SUPT3H from mammalian cells affects the transcription of only a specific subset of genes. Accordingly, in the absence of SUPT3H no major change in TBP accumulation at gene promoters was observed. Thus, SUPT3H is not required for the assembly of SAGA, TBP recruitment, or overall Pol II transcription, but plays a role in mESC growth and self-renewal. Our data further suggest that yeast and mammalian SAGA complexes contribute to transcription regulation by distinct mechanisms. In mammals, SAGA assembles without SUPT3H but unlike yeast, SUPT3H is not required for TBP deposition on promoters and global Pol II transcription, affecting only a subset of genes.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
11.4
作者：
de Jonge, Wim J.;O'Duibhir, Eoghan;Holstege, Frank C. P.
通讯作者：
Holstege, Frank C. P.
影响因子：
10.5
作者：
Antonova, Simona, V;Boeren, Jeffrey;Snel, Berend
通讯作者：
Snel, Berend
影响因子：
56.9
作者：
Chen, Xizi;Qi, Yilun;Xu, Yanhui
通讯作者：
Xu, Yanhui
影响因子：
64.5
作者：
Basehoar, AD;Zanton, SJ;Pugh, BF
通讯作者：
Pugh, BF