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The human CDK8 subcomplex is a molecular switch that controls Mediator coactivator function. A conserved Mediator–CDK8 kinase module association regulates Mediator–RNA polymerase II interaction. The cyclin-dependent kinase 8 module sterically blocks Mediator interactions with RNA polymerase II. Structures of transcription pre-initiation complex with TFIIH and Mediator. Structure of a complete Mediator–RNA polymerase II pre-initiation complex. Architecture of the RNA polymerase II–Mediator core initiation complex. Origins and activity of the Mediator complex. The metazoan Mediator co-activator complex as an integrative hub for transcriptional regulation. A multiprotein mediator of transcriptional activation and its interaction with the C-terminal repeat domain of RNA polymerase II. Structure and mechanism of the RNA polymerase II transcription machinery. Mediator and the mechanism of transcriptional activation. Transcriptional regulation through Mediator-like coactivators in yeast and metazoan cells. 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. 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. 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 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. 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 7, 8, 9. 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. 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 1, 2, 3, 4, 5, 6.

thinapp v 4.09 program is registered|rar|310 mb Mediator 9 .Mediator is a conserved coactivator complex that enables the regulated initiation of transcription at eukaryotic genes 1, 2, 3.

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