Mediator and SAGA Have Distinct Roles in Pol II Preinitiation Complex Assembly and Function

Xiao-Fen Chen; Lynn Lehmann; Justin J. Lin; Ajay Vashisht; Ryan Schmidt; Roberto Ferrari; Chengyang Huang; Robin McKee; Amber Mosley; Kathrin Plath; Siavash K. Kurdistani; James Wohlschlegel; Michael Carey

doi:10.1016/j.celrep.2012.10.019

Cell Reports (Nov 2012)

Mediator and SAGA Have Distinct Roles in Pol II Preinitiation Complex Assembly and Function

Xiao-Fen Chen,
Lynn Lehmann,
Justin J. Lin,
Ajay Vashisht,
Ryan Schmidt,
Roberto Ferrari,
Chengyang Huang,
Robin McKee,
Amber Mosley,
Kathrin Plath,
Siavash K. Kurdistani,
James Wohlschlegel,
Michael Carey

Affiliations

Xiao-Fen Chen: Department of Biological Chemistry, David Geffen School of Medicine, University of California, BSRB 351A, 615 Charles E. Young Drive, Los Angeles, CA 90095-1737, USA
Lynn Lehmann: Department of Biological Chemistry, David Geffen School of Medicine, University of California, BSRB 351A, 615 Charles E. Young Drive, Los Angeles, CA 90095-1737, USA
Justin J. Lin: Department of Biological Chemistry, David Geffen School of Medicine, University of California, BSRB 351A, 615 Charles E. Young Drive, Los Angeles, CA 90095-1737, USA
Ajay Vashisht: Department of Biological Chemistry, David Geffen School of Medicine, University of California, BSRB 351A, 615 Charles E. Young Drive, Los Angeles, CA 90095-1737, USA
Ryan Schmidt: Department of Biological Chemistry, David Geffen School of Medicine, University of California, BSRB 351A, 615 Charles E. Young Drive, Los Angeles, CA 90095-1737, USA
Roberto Ferrari: Department of Biological Chemistry, David Geffen School of Medicine, University of California, BSRB 351A, 615 Charles E. Young Drive, Los Angeles, CA 90095-1737, USA
Chengyang Huang: Department of Biological Chemistry, David Geffen School of Medicine, University of California, BSRB 351A, 615 Charles E. Young Drive, Los Angeles, CA 90095-1737, USA
Robin McKee: Department of Biological Chemistry, David Geffen School of Medicine, University of California, BSRB 351A, 615 Charles E. Young Drive, Los Angeles, CA 90095-1737, USA
Amber Mosley: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Room MS1021H, 635 Barnhill Drive, Indianapolis, IN 46202, USA
Kathrin Plath: Department of Biological Chemistry, David Geffen School of Medicine, University of California, BSRB 351A, 615 Charles E. Young Drive, Los Angeles, CA 90095-1737, USA
Siavash K. Kurdistani: Department of Biological Chemistry, David Geffen School of Medicine, University of California, BSRB 351A, 615 Charles E. Young Drive, Los Angeles, CA 90095-1737, USA
James Wohlschlegel: Department of Biological Chemistry, David Geffen School of Medicine, University of California, BSRB 351A, 615 Charles E. Young Drive, Los Angeles, CA 90095-1737, USA
Michael Carey: Department of Biological Chemistry, David Geffen School of Medicine, University of California, BSRB 351A, 615 Charles E. Young Drive, Los Angeles, CA 90095-1737, USA

DOI: https://doi.org/10.1016/j.celrep.2012.10.019
Journal volume & issue: Vol. 2, no. 5
pp. 1061 – 1067

Abstract

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A key feature of RNA polymerase II (Pol II) preinitiation complexes (PICs) is their ability to coordinate transcription initiation with chromatin modification and remodeling. To understand how this coordination is achieved, we employed extensive proteomic and mechanistic analyses to study the composition and assembly of PICs in HeLa cell and mouse embryonic stem cell (ESC) nuclear extracts. Strikingly, most of the machinery that is necessary for transcription initiation on chromatin is part of the PIC. The PIC is nearly identical between ESCs and HeLa cells and contains two major coactivator complexes: Mediator and SAGA. Genome-wide analysis of Mediator reveals that it has a close correlation with Pol II, TATA-binding protein, and messenger RNA levels and thus may play a major role in PIC assembly. Moreover, Mediator coordinates assembly of the Pol II initiation factors and chromatin machinery into a PIC in vitro, whereas SAGA acts after PIC assembly to allow transcription on chromatin.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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