STAGA recruits mediator to the MYC oncoprotein to stimulate transcription and cell proliferation
STAGA recruits mediator to the MYC oncoprotein to stimulate transcription and cell proliferation
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DOI：
10.1128/mcb.01402-07
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发表时间：
2008-01-01
影响因子：
5.3
通讯作者：
Martinez, Ernest
中科院分区：
文献类型：
--
作者：
Liu, Xiaohui;Vorontchikhina, Marina;Martinez, Ernest
真核基因转录的激活涉及多蛋白组蛋白乙酰转移酶（HAT）和介体复合物的DNA结合激活剂的募集。这些共激活因子复合物如何在功能上合作以及不同亚基/模块的作用仍不清楚。在这里，我们报告的人类HAT复合物STAGA（SPT 3-TAF 9-GCN 5-乙酰化酶）和“核心”形式的介体复合物在MYC癌蛋白的转录激活过程中的物理相互作用。人细胞中STAGA的STAF 65 γ组分的敲低阻止TRRAP和GCN 5与SPT 3和TAF 9亚基的稳定缔合;损害WC依赖性基因的转录，包括端粒酶逆转录酶（TERT）启动子的MYC反式激活;并抑制MYC依赖性细胞的增殖。STAF 65 γ是SPT 3/STAGA与核心介体相互作用以及SPT 3、TAF 9和核心介体组分向TERT启动子的MYC募集所需的，但对于TRRAP、GCN 5和p300的WC募集以及核小体的乙酰化和启动子上TFIID和RNA聚合酶II的加载是必需的。这些结果表明STAGA型复合物在细胞增殖和转录激活中通过TFIID和RNA聚合酶II的MYC后加载的新STAF 65 γ依赖性功能，其涉及核心介体的直接募集。
Activation of eukaryotic gene transcription involves the recruitment by DNA-binding activators of multiprotein histone acetyltransferase (HAT) and Mediator complexes. How these coactivator complexes functionally cooperate and the roles of the different subunits/modules remain unclear. Here we report physical interactions between the human HAT complex STAGA (SPT3-TAF9-GCN5-acetylase) and a "core" form of the Mediator complex during transcription activation by the MYC oncoprotein. Knockdown of the STAF65 gamma component of STAGA in human cells prevents the stable association of TRRAP and GCN5 with the SPT3 and TAF9 subunits; impairs transcription of WC-dependent genes, including MYC transactivation of the telomerase reverse transcriptase (TERT) promoter; and inhibits proliferation of MYC-dependent cells. STAF65 gamma is required for SPT3/STAGA interaction with core Mediator and for MYC recruitment of SPT3, TAF9, and core Mediator components to the TERT promoter but is dispensable for WC recruitment of TRRAP, GCN5, and p300 and for acetylation of nucleosomes and loading of TFIID and RNA polymerase II on the promoter. These results suggest a novel STAF65 gamma-dependent function of STAGA-type complexes in cell proliferation and transcription activation by MYC postloading of TFIID and RNA polymerase II that involves direct recruitment of core Mediator.