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TitleStructure of the human Mediator-bound transcription preinitiation complex.
Journal, issue, pagesScience, Vol. 372, Issue 6537, Page 52-56, Year 2021
Publish dateApr 2, 2021
AuthorsR Abdella / A Talyzina / S Chen / C J Inouye / R Tjian / Y He /
PubMed AbstractEukaryotic 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 ...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.
External linksScience / PubMed:33707221 / PubMed Central
MethodsEM (single particle)
Resolution3.4 - 7.1 Å
Structure data

23255

7lbm

EMDB-23255, PDB-7lbm:
Structure of the human Mediator-bound transcription pre-initiation complex
Method: EM (single particle) / Resolution: 4.8 Å

EMDB-23256:
Focused refinement on the cPIC within the human Mediator-bound transcription pre-initiation complex
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-23257:
Focused refinement of cTFIIH within the human Mediator-bound transcription pre-initiation complex
Method: EM (single particle) / Resolution: 7.1 Å

EMDB-23258:
Focused refinement on the Mediator Head module within the human Mediator-bound transcription pre-initiation complex
Method: EM (single particle) / Resolution: 4.0 Å

EMDB-23259:
Focused refinement of the Mediator Middle module and TFIIH CAK module within the human Mediator-bound transcription pre-initiation complex
Method: EM (single particle) / Resolution: 6.5 Å

EMDB-23260:
Focused refinement on the Med14 C-terminus within the human Mediator-bound transcription pre-initiation complex
Method: EM (single particle) / Resolution: 4.0 Å

EMDB-23261:
Focused refinement on the Mediator Tail module within the human Mediator-bound transcription pre-initiation complex
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-23262:
Focused refinement on Med1 within the human Mediator-bound transcription pre-initiation complex
Method: EM (single particle) / Resolution: 5.8 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ZN:
Unknown entry

ChemComp-SF4:
IRON/SULFUR CLUSTER / Iron–sulfur cluster

Source
  • homo sapiens (human)
  • Human (human)
KeywordsTRANSCRIPTION/DNA / pre-initiation complex / Mediator / initiation / complex / transcription / TRANSCRIPTION-DNA complex

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