Structures of the human Mediator and Mediator-bound preinitiation complex

被引：112

作者：

Chen, Xizi ^{[1
,2
]}

Yin, Xiaotong ^{[1
,2
]}

Li, Jiabei ^{[1
,2
]}

Wu, Zihan ^{[1
,2
]}

Qi, Yilun ^{[1
,2
]}

Wang, Xinxin ^{[1
,2
]}

Liu, Weida ^{[1
,2
]}

Xu, Yanhui ^{[1
,2
,3
,4
,5
]}

机构：

[1] Fudan Univ, Shanghai Canc Ctr, Inst Biomed Sci, State Key Lab Genet Engn,Shanghai Key Lab Radiat, Shanghai, Peoples R China

[2] Fudan Univ, Shanghai Key Lab Med Epigenet, Shanghai Med Coll, Shanghai 200032, Peoples R China

[3] Minist Sci & Technol China, Int Colab Med Epigenet & Metab, Beijing, Peoples R China

[4] Fudan Univ, Sch Basic Med Sci, Dept Syst Biol Med, Shanghai Med Coll, Shanghai 200032, Peoples R China

[5] Fudan Univ, Collaborat Innovat Ctr Genet & Dev, Sch Life Sci, Human Phenome Inst, Shanghai 200433, Peoples R China

来源：

SCIENCE | 2021年 / 372卷 / 6546期

关键词：

RNA-POLYMERASE-II; TERMINAL REPEAT DOMAIN; CDK-ACTIVATING KINASE; CRYSTAL-STRUCTURE; TAIL MODULE; TRANSCRIPTION; INITIATION; SUBUNIT; ARCHITECTURE; PROMOTER;

D O I：

10.1126/science.abg0635

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The 1.3-megadalton transcription factor IID (TFIID) is required for preinitiation complex (PIC) assembly and RNA polymerase II (Pol II)-mediated transcription initiation on almost all genes. The 26-subunit Mediator stimulates transcription and cyclin-dependent kinase 7 (CDK7)-mediated phosphorylation of the Pol II C-terminal domain (CTD). We determined the structures of human Mediator in the Tail module-extended (at near-atomic resolution) and Tail-bent conformations and structures of TFIID-based PICMediator (76 polypeptides, similar to 4.1 megadaltons) in four distinct conformations. PIC-Mediator assembly induces concerted reorganization (Head-tilting and Middle-down) of Mediator and creates a Head-Middle sandwich, which stabilizes two CTD segments and brings CTD to CDK7 for phosphorylation; this suggests a CTD-gating mechanism favorable for phosphorylation. The TFIID-based PIC architecture modulates Mediator organization and TFIIH stabilization, underscoring the importance of TFIID in orchestrating PIC-Mediator assembly.

引用

页码：1055 / +

页数：63

共 104 条

[1] Structure of the human Mediator-bound transcription preinitiation complex [J].