Mediator and SAGA have distinct roles in Pol II preinitiation complex assembly and function
Xiao-Fen Chen1, Lynn Lehmann, Justin J Lin
1Department of Biological Chemistry, David Geffen School of Medicine, University of California, BSRB 351A, 615 Charles E. Young Drive, Los Angeles, CA 90095-1737, USA.
Cell Reports
|November 27, 2012
Summary
The preinitiation complex (PIC) coordinates transcription initiation with chromatin modification. Mediator and SAGA are key coactivator complexes within the PIC, with Mediator crucial for its assembly and SAGA for chromatin transcription.
Area of Science:
- Molecular Biology
- Gene Regulation
- Chromatin Biology
Background:
- RNA polymerase II (Pol II) preinitiation complexes (PICs) coordinate transcription initiation with chromatin modification and remodeling.
- Understanding the composition and assembly of PICs is crucial for elucidating gene regulation.
Purpose of the Study:
- To investigate the composition and assembly of Pol II PICs using proteomic and mechanistic analyses.
- To determine the roles of coactivator complexes like Mediator and SAGA in PIC formation and function.
Main Methods:
- Proteomic analyses of PICs in HeLa cell and mouse embryonic stem cell (ESC) nuclear extracts.
- Mechanistic studies to analyze PIC assembly and the function of coactivator complexes.
Main Results:
- PICs are nearly identical in ESCs and HeLa cells, containing Mediator and SAGA coactivator complexes.
- Most transcription initiation machinery on chromatin is part of the PIC.
- Mediator correlates with Pol II, TATA-binding protein, and mRNA levels, suggesting a key role in PIC assembly.
- Mediator coordinates the assembly of Pol II initiation factors and chromatin machinery, while SAGA acts post-assembly for chromatin transcription.
Conclusions:
- The PIC is a highly conserved and integrated machinery for transcription initiation.
- Mediator plays a central role in assembling the PIC, while SAGA facilitates transcription on chromatin.
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