Mediator is an intrinsic component of the basal RNA polymerase II machinery in vivo

Lacombe, Thierry; Poh, Siew Lay; Barbey, Régine; Kuras, Laurent

doi:10.1093/nar/gkt701

Cited by 25 publications

(30 citation statements)

References 56 publications

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“…Mediator supports TFIIB binding to promoters, and both Mediator and TFIIB facilitate recruitment of RNAPII to promoter-bound GTFs (30). This notion is in agreement with both older and more recent studies in yeast (43,71,80,81), murine (82), and human cells (83) which indicate concurrent interactions of Mediator, TFIIB, and RNAPII. MS data from S.cerevisiae and from human cells identify RNAPII, TFIIB, and TFIIF among the strongest interactors of Mediator (71,83), and these factors are necessary for reinitiation (25).…”

Section: Discussionsupporting

confidence: 88%

PPARβ/δ controls Mediator recruitment and transcription initiation

Legrand

Zielke

et al. 2019

Preprint

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In the absence of ligands, the nuclear receptor PPARβ/δ recruits the NCOR and SMRT corepressors, which form complexes with HDAC3, to canonical target genes. Agonistic ligands cause dissociation of corepressors and enable enhanced transcription. Vice versa, synthetic inverse agonists augment corepressor recruitment and repression. Both basal repression of the target gene ANGPTL4 and reinforced repression elicited by inverse agonists are partially insensitive to HDAC inhibition. This raises the question of how PPARβ/δ represses transcription mechanistically. We show that the PPARβ/δ inverse agonist PT-S264 impairs transcription initiation by decreasing recruitment of activating Mediator subunits, RNA polymerase II, and TFIIB, but not of TFIIA, to the ANGPTL4 promoter. Mass spectrometry identifies NCOR as the main PT-S264-dependent interactor of PPARβ/δ.

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Section: Discussionsupporting

confidence: 88%

PPARβ/δ controls Mediator recruitment and transcription initiation

Legrand

Zielke

et al. 2019

Preprint

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“…ing it may be regarded as part of the general transcription machinery (5)(6)(7). In addition to its role in PIC recruitment, Mediator also plays a role at some promoters in the recruitment of other co-activator complexes.…”

mentioning

confidence: 99%

Mediator, TATA-binding Protein, and RNA Polymerase II Contribute to Low Histone Occupancy at Active Gene Promoters in Yeast

Ansari

Paul

Sommer

et al. 2014

Journal of Biological Chemistry

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Background:Promoters of active genes in eukaryotes are typically depleted of histone proteins. Results: Histone eviction from the induced CHA1 promoter is compromised by mutations in transcription factors, and higher histone occupancy is also seen at constitutively active promoters in such mutants. Conclusion: Preinitiation complex formation promotes reduced histone occupancy at active gene promoters. Significance: Preinitiation complex components participate in chromatin remodeling.

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“…The absence of prominent upstream Mediator peaks at most TFIID-regulated, tail module-independent promoters, in spite of the presence of Mediator at proximal promoter regions of these genes (10,11,17), underscores the possibility that Mediator is recruited to such targets by a distinct mechanism from that used at SAGA-regulated, tail module-dependent genes (38). Mediator can evidently be recruited in part via interactions with the general transcription machinery (39,40); such a mechanism could be consistent with patterns of Mediator occupancy that we observe here at TFIID-regulated, tail moduleindependent genes ( Fig. 3; Mediator has been reported to be associated with transcribed ORFs in both S. cerevisiae and S. pombe (7,9).…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Association of Mediator and RNA Polymerase II in Wild-Type and Mediator Mutant Yeast

Paul

Zhu

Landsman

et al. 2015

Molecular and Cellular Biology

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cMediator is a large, multisubunit complex that is required for essentially all mRNA transcription in eukaryotes. In spite of the importance of Mediator, the range of its targets and how it is recruited to these is not well understood. Previous work showed that in Saccharomyces cerevisiae, Mediator contributes to transcriptional activation by two distinct mechanisms, one depending on the tail module triad and favoring SAGA-regulated genes, and the second occurring independently of the tail module and favoring TFIID-regulated genes. Here, we use chromatin immunoprecipitation sequencing (ChIP-seq) to show that dependence on tail module subunits for Mediator recruitment and polymerase II (Pol II) association occurs preferentially at SAGA-regulated over TFIID-regulated genes on a genome-wide scale. We also show that recruitment of tail module subunits to active gene promoters continues genome-wide when Mediator integrity is compromised in med17 temperature-sensitive (ts) yeast, demonstrating the modular nature of the Mediator complex in vivo. In addition, our data indicate that promoters exhibiting strong and stable occupancy by Mediator have a wide range of activity and are enriched for targets of the Tup1-Cyc8 repressor complex. We also identify a number of strong Mediator occupancy peaks that overlap dubious open reading frames (ORFs) and are likely to include previously unrecognized upstream activator sequences.

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Mediator is an intrinsic component of the basal RNA polymerase II machinery in vivo

Cited by 25 publications

References 56 publications

PPARβ/δ controls Mediator recruitment and transcription initiation

PPARβ/δ controls Mediator recruitment and transcription initiation

Mediator, TATA-binding Protein, and RNA Polymerase II Contribute to Low Histone Occupancy at Active Gene Promoters in Yeast

Genome-Wide Association of Mediator and RNA Polymerase II in Wild-Type and Mediator Mutant Yeast

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