A Mediator-responsive form of metazoan RNA polymerase II

Hu, Xiaopeng; Malik, Sohail; Negroiu, Costin Catalin; Hubbard, Kyle; Velalar, Chidambaram Natesa; Hampton, Brian; Grosu, Dan; Catalano, Jennifer; Roeder, Robert G.; Gnatt, Averell

doi:10.1073/pnas.0603702103

Cited by 78 publications

(117 citation statements)

References 55 publications

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“…Thus, in as much as the Mediator (and TFIIB) can reverse each of those DSIF effects, one can infer that they likely also control these various steps. Importantly, together with a recent report identifying Gdown1 as another factor that determines Mediator dependencies (30), it seems that sensing of total ''transcriptional flux'' may be generally important in the specification of a Mediator requirement. Thus when transcriptional flux is high there would neither be any need nor an opportunity for Mediator function.…”

Section: Discussionmentioning

confidence: 99%

Identification of a regulator of transcription elongation as an accessory factor for the human Mediator coactivator

Malik

Barrero

Jones

2007

Proc. Natl. Acad. Sci. U.S.A.

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The multiprotein Mediator coactivator complex is universally required for transcription of metazoan genes. It has been proposed to function by interfacing between transcriptional activators and the RNA polymerase II machinery. However, in vitro transcription systems reconstituted from homogeneous preparations of RNA polymerase II, the general transcription initiation factors, and the cofactor PC4 display relatively robust activator (HNF-4)-dependent activity, which, nonetheless, can be further stimulated by Mediator. By contrast, an unfractionated nuclear extract-based system in which Mediator has been immunodepleted displays a nearabsolute dependence on ectopic Mediator. Here, we identified and purified an activity, MSA-2, that confers extract-like Mediator responsiveness to our reconstituted system. Mass spectrometric analyses identified its two constituent polypeptides as hSpt5 and hSpt4, which also comprise the elongation factor DSIF. Mechanistically, MSA-2/DSIF acts by restricting overall transcription in the pure system, thereby imposing a strong Mediator dependence. Our data thus point to potential mechanisms for Mediator function beyond its presently believed role in promoting the initial formation of the RNA polymerase II-containing preinitiation complex.DRB sensitivity-inducing factor ͉ hepatocyte nuclear factor-4 ͉ positive cofactor 2 ͉ RNA polymerase II

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Section: Discussionmentioning

confidence: 99%

Identification of a regulator of transcription elongation as an accessory factor for the human Mediator coactivator

Malik

Barrero

Jones

2007

Proc. Natl. Acad. Sci. U.S.A.

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“…1). 5,6,24,36 RPRD1A and RPRD1B likewise co-purified with each other as well as with RPRD2 (Fig. 1).…”

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confidence: 99%

Control of the RNA polymerase II phosphorylation state in promoter regions by CTD interaction domain-containing proteins RPRD1A and RPRD1B

Ni¹,

Olsen²,

Guo³

et al. 2011

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“…Since then, its composition and function have been shown to be conserved in Drosophila, mouse, and human cells (1)(2)(3). The mediator complex can directly bind to Pol II and recruit it to target promoters (4-6), but it also appears to function at a step subsequent to Pol II assembly into the preinitiation complex (7,8). Several mediator subunits have been shown to act as adaptors for specific transcription factors, linking them to the mediator complex and allowing them to activate transcription (9)(10)(11)(12)(13)(14).…”

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confidence: 99%

Pygopus activates Wingless target gene transcription through the mediator complex subunits Med12 and Med13

Carrera

Janody

Leeds

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Wnt target gene transcription is mediated by nuclear translocation of stabilized ␤-catenin, which binds to TCF and recruits Pygopus, a cofactor with an unknown mechanism of action. The mediator complex is essential for the transcription of RNA polymerase II-dependent genes; it associates with an accessory subcomplex consisting of the Med12, Med13, Cdk8, and Cyclin C subunits. We show here that the Med12 and Med13 subunits of the Drosophila mediator complex, encoded by kohtalo and skuld, are essential for the transcription of Wingless target genes. kohtalo and skuld act downstream of ␤-catenin stabilization both in vivo and in cell culture. They are required for transcriptional activation by the N-terminal domain of Pygopus, and their physical interaction with Pygopus depends on this domain. We propose that Pygopus promotes Wnt target gene transcription by recruiting the mediator complex through interactions with Med12 and Med13.Drosophila ͉ kinase module ͉ kohtalo ͉ skuld ͉ Wnt

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A Mediator-responsive form of metazoan RNA polymerase II

Cited by 78 publications

References 55 publications

Identification of a regulator of transcription elongation as an accessory factor for the human Mediator coactivator

Identification of a regulator of transcription elongation as an accessory factor for the human Mediator coactivator

Control of the RNA polymerase II phosphorylation state in promoter regions by CTD interaction domain-containing proteins RPRD1A and RPRD1B

Pygopus activates Wingless target gene transcription through the mediator complex subunits Med12 and Med13

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