Unknown,Transcriptomics,Genomics,Proteomics

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Regulation of Mediator-dependent transcriptional activation of Pol II(G) through TFII


ABSTRACT: Pol II(G) is a novel form of RNA polymerase II that contains a tightly associated Gdown1 polypeptide. Whereas Pol II suffices for robust activator-dependent transcription in the absence of Mediator, Pol II(G) is highly dependent upon Mediator in a biochemically defined in vitro system. However, the mechanism(s) whereby Gdown1 alters the coactivator-dependence of Pol II is unknown. Here we show that Gdown1 competes with TFIIF for binding to the RPB1 and RPB5 subunits of Pol II in vitro, resulting in inhibition of a critical function of TFIIF in facilitating PIC assembly. The apparent inability of Pol II(G) to associate with TFIIF suggests that Gdown1 must be removed from Pol II for transcription initiation. However, Mediator can actually help Pol II(G) bind to the promoter prior to subsequent Mediator functions. Complementary cell-based analyses reveal that Pol II(G) is recruited to promoter regions of subsets of actively transcribed genes, where Pol II(G) appears to modulate transcription. Our findings indicate that differential regulation of subsets of genes by Pol II and Pol II(G) occurs through the regulation of TFIIF and consequent alterations in Mediator requirements. Genome-wide localization of PolII and Gdown1 in human IMR90 fibroblast cells using ChIP-seq

ORGANISM(S): Homo sapiens

SUBMITTER: Ulrich Wagner 

PROVIDER: E-GEOD-33128 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Transcriptional regulation by Pol II(G) involving mediator and competitive interactions of Gdown1 and TFIIF with Pol II.

Jishage Miki M   Malik Sohail S   Wagner Ulrich U   Uberheide Beatrix B   Ishihama Yasushi Y   Hu Xiaopeng X   Chait Brian T BT   Gnatt Averell A   Ren Bing B   Roeder Robert G RG  

Molecular cell 20120101 1


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  ...[more]

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