RNA polymerase II subunit D / DNA-directed RNA polymerase II subunit RPB11-a / DNA-directed RNA polymerases I, II, and III subunit RPABC3 / DNA-directed RNA polymerases I, II, and III subunit RPABC5 / Mediator of RNA polymerase II transcription subunit 19 / DNA-directed RNA polymerases I, II, and III subunit RPABC2 / DNA-directed RNA polymerase II subunit RPB3 / DNA-directed RNA polymerase subunit beta / DNA-directed RNA polymerase II subunit RPB7 / RNA polymerase II, I and III subunit K ...RNA polymerase II subunit D / DNA-directed RNA polymerase II subunit RPB11-a / DNA-directed RNA polymerases I, II, and III subunit RPABC3 / DNA-directed RNA polymerases I, II, and III subunit RPABC5 / Mediator of RNA polymerase II transcription subunit 19 / DNA-directed RNA polymerases I, II, and III subunit RPABC2 / DNA-directed RNA polymerase II subunit RPB3 / DNA-directed RNA polymerase subunit beta / DNA-directed RNA polymerase II subunit RPB7 / RNA polymerase II, I and III subunit K / DNA-directed RNA polymerase II subunit E / Mediator of RNA polymerase II transcription subunit 7 / Mediator of RNA polymerase II transcription subunit 14 / Mediator of RNA polymerase II transcription subunit 6 / General transcription factor IIF subunit 2 / General transcription and DNA repair factor IIH helicase subunit XPD / General transcription and DNA repair factor IIH helicase subunit XPB / TATA-box-binding protein / General transcription factor IIE subunit 1 / Transcription initiation factor IIE subunit beta / General transcription factor IIH subunit 1 / General transcription factor IIF subunit 1 / Cyclin-dependent kinase 7 / Cyclin-H / CDK-activating kinase assembly factor MAT1 / Transcription initiation factor IIA subunit 1 / Transcription initiation factor IIA subunit 2 / DNA-directed RNA polymerase II subunit RPB9 / Transcription initiation factor IIB / Mediator of RNA polymerase II transcription subunit 21 / General transcription factor IIH subunit 2 / General transcription factor IIH subunit 3 / Mediator of RNA polymerase II transcription subunit 22 / Mediator of RNA polymerase II transcription subunit 27 / General transcription factor IIH subunit 5 / General transcription factor IIH subunit 4 / Mediator of RNA polymerase II transcription subunit 8 / Mediator of RNA polymerase II transcription subunit 30 / Mediator of RNA polymerase II transcription subunit 10 / Mediator of RNA polymerase II transcription subunit 18 / Mediator of RNA polymerase II transcription subunit 28 / Mediator of RNA polymerase II transcription subunit 20 / Mediator of RNA polymerase II transcription subunit 4 / Mediator of RNA polymerase II transcription subunit 17 / Mediator of RNA polymerase II transcription subunit 9 / Mediator of RNA polymerase II transcription subunit 11 / Mediator of RNA polymerase II transcription subunit 31 類似検索 - 構成要素
H2020 Marie Curie Actions of the European Commission
894862
European Union
German Research Foundation (DFG)
EXC 2067/1 39072994
ドイツ
European Research Council (ERC)
882357
European Union
German Research Foundation (DFG)
SFB860
ドイツ
German Research Foundation (DFG)
SPP2191
ドイツ
引用
ジャーナル: Nature / 年: 2021 タイトル: Structure of the human Mediator-RNA polymerase II pre-initiation complex. 著者: Srinivasan Rengachari / Sandra Schilbach / Shintaro Aibara / Christian Dienemann / Patrick Cramer / 要旨: Mediator is a conserved coactivator complex that enables the regulated initiation of transcription at eukaryotic genes. Mediator is recruited by transcriptional activators and binds the pre- ...Mediator is a conserved coactivator complex that enables the regulated initiation of transcription at eukaryotic genes. Mediator is recruited by transcriptional activators and binds the pre-initiation complex (PIC) to stimulate the phosphorylation of RNA polymerase II (Pol II) and promoter escape. Here we prepare a recombinant version of human Mediator, reconstitute a 50-subunit Mediator-PIC complex and determine the structure of the complex by cryo-electron microscopy. The head module of Mediator contacts the stalk of Pol II and the general transcription factors TFIIB and TFIIE, resembling the Mediator-PIC interactions observed in the corresponding complex in yeast. The metazoan subunits MED27-MED30 associate with exposed regions in MED14 and MED17 to form the proximal part of the Mediator tail module that binds activators. Mediator positions the flexibly linked cyclin-dependent kinase (CDK)-activating kinase of the general transcription factor TFIIH near the linker to the C-terminal repeat domain of Pol II. The Mediator shoulder domain holds the CDK-activating kinase subunit CDK7, whereas the hook domain contacts a CDK7 element that flanks the kinase active site. The shoulder and hook domains reside in the Mediator head and middle modules, respectively, which can move relative to each other and may induce an active conformation of the CDK7 kinase to allosterically stimulate phosphorylation of the C-terminal domain.