Transcriptional Regulation by Pol II(G) Involving Mediator and Competitive Interactions of Gdown1 and TFIIF with Pol II

Pol II(G) is a distinct form of RNA polymerase II that contains the tightly associated Gdown1 polypeptide (encoded by POLR2M). Unlike Pol II, Pol II(G) is highly dependent upon Mediator for robust activator-dependent transcription in a biochemically defined in vitro system. Here, in vitro studies sh...

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Bibliographic Details
Published in:Molecular cell 2012-01, Vol.45 (1), p.51-63
Main Authors: Jishage, Miki, Malik, Sohail, Wagner, Ulrich, Uberheide, Beatrix, Ishihama, Yasushi, Hu, Xiaopeng, Chait, Brian T., Gnatt, Averell, Ren, Bing, Roeder, Robert G.
Format: Article
Language:English
Subjects:
Binding, Competitive
DNA-directed RNA polymerase
DNA-Directed RNA Polymerases - metabolism
Gene Expression Regulation
genes
HeLa Cells
Humans
in vitro studies
Mediator Complex - metabolism
Mediator Complex - physiology
polypeptides
promoter regions
RNA interference
RNA Polymerase II - genetics
RNA Polymerase II - metabolism
RNA Polymerase II - physiology
transcription (genetics)
Transcription Factors, TFII - genetics
Transcription Factors, TFII - metabolism
Transcription Factors, TFII - physiology
Transcription, Genetic
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Summary:Pol II(G) is a distinct form of RNA polymerase II that contains the tightly associated Gdown1 polypeptide (encoded by POLR2M). Unlike Pol II, Pol II(G) is highly dependent upon Mediator for robust activator-dependent transcription in a biochemically defined in vitro system. Here, in vitro studies show that Gdown1 competes with TFIIF for binding to the RPB1 and RPB5 subunits of Pol II, thereby inhibiting an essential function of TFIIF in preinitiation complex assembly, but also that Mediator can actually facilitate Pol II(G) binding to the promoter prior to subsequent Mediator functions. Complementary ChIP and RNAi analyses reveal that Pol II(G) is recruited to promoter regions of subsets of actively transcribed genes, where it appears to restrict transcription. These and other results suggest that Pol II(G) may act to modulate some genes while simultaneously, as a poised (noninitiated) polymerase, setting the stage for Mediator-dependent enhancement of their activity. ► Gdown1 downregulates transcription by competing with TFIIF for binding to Pol II ► Mediator is required for PIC assembly entailing Pol II(G) ► Pol II(G) is recruited to promoter regions in vivo to regulate gene transcription ► Pol II(G) is a poised but not initiated Pol II
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2011.12.014