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Structure of the human Mediator-bound transcription preinitiation complex.

Abdella R, Talyzina A, Chen S, Inouye CJ, Tjian R, He Y
Science 372 52-56 (2021)
Cited: 61 times
EuropePMC logo PMID: 33707221

Abstract

Eukaryotic transcription requires the assembly of a multisubunit preinitiation complex (PIC) composed of RNA polymerase II (Pol II) and the general transcription factors. The coactivator Mediator is recruited by transcription factors, facilitates the assembly of the PIC, and stimulates phosphorylation of the Pol II C-terminal domain (CTD) by the TFIIH subunit CDK7. Here, we present the cryo-electron microscopy structure of the human Mediator-bound PIC at a resolution below 4 angstroms. Transcription factor binding sites within Mediator are primarily flexibly tethered to the tail module. CDK7 is stabilized by multiple contacts with Mediator. Two binding sites exist for the Pol II CTD, one between the head and middle modules of Mediator and the other in the active site of CDK7, providing structural evidence for Pol II CTD phosphorylation within the Mediator-bound PIC.

Reviews - 7lbm mentioned but not cited (1)

  1. Assembly of RNA polymerase II transcription initiation complexes. Farnung L, Vos SM. Curr Opin Struct Biol 73 102335 (2022)

Articles - 7lbm mentioned but not cited (3)



Reviews citing this publication (17)

  1. The Mediator complex as a master regulator of transcription by RNA polymerase II. Richter WF, Nayak S, Iwasa J, Taatjes DJ. Nat Rev Mol Cell Biol 23 732-749 (2022)
  2. Targeting transcription cycles in cancer. Vervoort SJ, Devlin JR, Kwiatkowski N, Teng M, Gray NS, Johnstone RW. Nat Rev Cancer 22 5-24 (2022)
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  5. Genomic regulation of transcription and RNA processing by the multitasking Integrator complex. Welsh SA, Gardini A. Nat Rev Mol Cell Biol 24 204-220 (2023)
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  8. Regulation of the RNA polymerase II pre-initiation complex by its associated coactivators. Malik S, Roeder RG. Nat Rev Genet 24 767-782 (2023)
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  10. Transcription factor IID parks and drives preinitiation complexes at sharp or broad promoters. Bernardini A, Hollinger C, Willgenss D, Müller F, Devys D, Tora L. Trends Biochem Sci 48 839-848 (2023)
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  12. Enhancer selectivity in space and time: from enhancer-promoter interactions to promoter activation. Yang JH, Hansen AS. Nat Rev Mol Cell Biol 25 574-591 (2024)
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