Human mediator subunit MED26 functions as a docking site for transcription elongation factors.

Human mediator subunit MED26 functions as a docking site for transcription elongation factors.
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DOI:
10.1016/j.cell.2011.06.005
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发表时间:
2011-07-08
期刊:
影响因子:
64.5
通讯作者:
Conaway JW
Conaway JW
中科院分区:
生物学1区
文献类型:
--
作者:
Takahashi H;Parmely TJ;Sato S;Tomomori-Sato C;Banks CA;Kong SE;Szutorisz H;Swanson SK;Martin-Brown S;Washburn MP;Florens L;Seidel CW;Lin C;Smith ER;Shilatifard A;Conaway RC;Conaway JW

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启动子近端暂停由启动RNA聚合酶II (Pol II)和调控释放暂停聚合酶到生产延伸已成为转录激活的主要机制。暂停的Pol II的再激活与含有ELL/EAF家族成员,P-TEFb和其他蛋白质的SuperElongationComplexes (SECs)的招募相关,但其招募机制目前是一个主要的未解之谜。在这里,我们提出证据证明人类中介亚基Med26在这一过程中发挥作用。我们在Med26的保守n端域中发现了SEC和第二个含有ELL/ eaf的复合物以及一般起始因子TFIID的重叠对接位点。此外,我们提供了与模型一致的证据,即Med26可以作为一个分子开关,首先与Pol II起始复合物中的TFIID相互作用,然后将TFIID交换为含有ELL/EAF和P-TEFb的复合物,以促进Pol II过渡到转录的延伸阶段。
Promoter proximal pausing by initiated RNA polymerase II (Pol II) and regulated release of paused polymerase into productive elongation has emerged as a major mechanism of transcription activation. Reactivation of paused Pol II correlates with recruitment of SuperElongationComplexes (SECs) containing ELL/EAF family members, P-TEFb, and other proteins, but the mechanism of their recruitment is currently a major unanswered question. Here, we present evidence for a role of human Mediator subunit Med26 in this process. We identify in the conserved N-terminal domain of Med26 overlapping docking sites for SEC and a second ELL/EAF-containing complex, as well as general initiation factor TFIID. In addition, we present evidence consistent with the model that Med26 can function as a molecular switch that interacts first with TFIID in the Pol II initiation complex and then exchanges TFIID for complexes containing ELL/EAF and P-TEFb to facilitate transition of Pol II into the elongation stage of transcription.
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