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DOI	10.1126/science.abg0635
	Structures of the human Mediator and Mediator-bound preinitiation complex
	Chen X.; Yin X.; Li J.; Wu Z.; Qi Y.; Wang X.; Liu W.; Xu Y.
发表日期	2021
ISSN	0036-8075
卷号	372 期号:6546
英文摘要	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 PIC-Mediator (76 polypeptides, ~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. © 2021 American Association for the Advancement of Science. All rights reserved.
英文关键词	cyclin dependent kinase 7; DNA fragment; glutaraldehyde; glycerol; proteinase inhibitor; RNA polymerase II; TATA binding protein; transcription factor; transcription factor IID; transcription factor IIH; cyclin dependent kinase; cyclin-dependent kinase-activating kinase; DNA binding protein; DNA helicase; MED1 protein, human; MED14 protein, human; MED15 protein, human; Med17 protein, human; mediator complex; peroxisome proliferator activated receptor binding protein; protein binding; RNA polymerase II; transcription factor IID; transcription factor IIH; XPBC-ERCC-3 protein; chemical reaction; enzyme; enzyme activity; gene expression; induced response; polymer; stabilization; anion exchange chromatography; Article; assay; autoradiography; carboxy terminal sequence; centrifugation; controlled study; cross linking; cryoelectron microscopy; crystal structure; electron microscopy; expression vector; head tilting; human; hydrogen bond; image analysis; image processing; imaging and display; immunoprecipitation; in vitro transcription assay; ion exchange chromatography; mass spectrometry; molecular dynamics; nonhuman; open reading frame; polyacrylamide gel electrophoresis; protein aggregation; protein conformation; protein expression; protein expression level; protein phosphorylation; protein protein interaction; sequence analysis; silver staining; stoichiometry; transcription initiation; alpha helix; chemistry; metabolism; molecular model; phosphorylation; promoter region; protein domain; protein folding; protein quaternary structure; protein subunit; transcription initiation; Cryoelectron Microscopy; Cyclin-Dependent Kinases; DNA Helicases; DNA-Binding Proteins; Humans; Mediator Complex; Mediator Complex Subunit 1; Models, Molecular; Phosphorylation; Promoter Regions, Genetic; Protein Binding; Protein Conformation, alpha-Helical; Protein Domains; Protein Folding; Protein Structure, Quaternary; Protein Subunits; RNA Polymerase II; Transcription Factor TFIID; Transcription Factor TFIIH; Transcription Initiation, Genetic
语种	英语
来源期刊	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/243307
作者单位	Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Radiation Oncology, Shanghai Key Laboratory of Medical Epigenetics, Shanghai Medical College of Fudan University, Shanghai, 200032, China; International Co-Laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, China, Department of Systems Biology for Medicine, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, 200032, China; Human Phenome Institute, Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Fudan University, Shanghai, 200433, China
推荐引用方式 GB/T 7714	Chen X.,Yin X.,Li J.,et al. Structures of the human Mediator and Mediator-bound preinitiation complex[J],2021,372(6546).
APA	Chen X..,Yin X..,Li J..,Wu Z..,Qi Y..,...&Xu Y..(2021).Structures of the human Mediator and Mediator-bound preinitiation complex.Science,372(6546).
MLA	Chen X.,et al."Structures of the human Mediator and Mediator-bound preinitiation complex".Science 372.6546(2021).