Proteomic Analysis of the Mediator Complex Interactome in Saccharomyces cerevisiae

Uthe, Henriette; Vanselow, Jens T.; Schlösser, Andreas

doi:10.1038/srep43584

Cited by 24 publications

(19 citation statements)

References 66 publications

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“…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). Notably, another recent study revealed that human genes which require de novo RNAPII recruitment for induction of transcription depend on TFIIB availability (84).…”

Section: Discussionsupporting

confidence: 92%

“…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%

“…We speculate that acetyltransferases are inhibited by NCOR and SMRT complexes since (i) acetyltransferase activity is required for transcription in nucleosome-free systems (66), (ii) GTFs that contribute to reinitiation-TFIIB, TFIIE, and TFIIF-are acetylated in vivo (67,68), and (iii) the acetyltransferase activities of CBP and p300 are inhibited by recombinant purified fragments of NCOR and SMRT in vitro (69,70). Moreover, Mediator interacts with the acetyltransferasebearing SAGA complex, and both Mediator and SAGA are necessary for RNAPII-mediated transcription in yeast (71,72,73). Partial sensitivity of PT-S264dependent repression to HDAC inhibitors ( fig.…”

Section: Discussionmentioning

confidence: 99%

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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: 92%

Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

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PPARβ/δ controls Mediator recruitment and transcription initiation

Legrand

Zielke

et al. 2019

Preprint

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“…One possible mechanism for recruitment of Mediator to sn/snoRNAs is via the interaction of activators, including Tbf1, with other subunits of Mediator, such as the tail/middle module connector Med16, which interacts with activators such as Gcn4 in yeast (49), DIF in Drosophila (53), and NRF2 in mouse and human (54). Indeed, a recent proteomic analysis of Mediator interactions reported a modest interaction between Mediator and Tbf1 (55). Mediator could also be recruited to sn/snoRNA genes independently of activators via interactions with the PIC (34,(56)(57)(58).…”

Section: Discussionmentioning

confidence: 99%

Mediator Is Essential for Small Nuclear and Nucleolar RNA Transcription in Yeast

Tourigny

Saleh

Schumacher

et al. 2018

Molecular and Cellular Biology

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Eukaryotic RNA polymerase II (RNAPII) transcribes mRNA genes and non-protein-coding RNA (ncRNA) genes, including those encoding small nuclear and nucleolar RNAs (sn/snoRNAs). In metazoans, RNAPII transcription of sn/snoRNAs is facilitated by a number of specialized complexes, but no such complexes have been discovered in yeast. It has been proposed that yeast sn/snoRNA and mRNA expression relies on a set of common factors, but the extent to which regulators of mRNA genes function at yeast sn/snoRNA genes is unclear. Here, we investigated a potential role for the Mediator complex, essential for mRNA gene transcription, in sn/ snoRNA gene transcription. We found that Mediator maps to sn/snoRNA gene regulatory regions and that rapid depletion of the essential structural subunit Med14 strongly reduces RNAPII and TFIIB occupancy as well as nascent transcription of sn/ snoRNA genes. Deletion of Med3 and Med15, subunits of the activator-interacting Mediator tail module, does not affect Mediator recruitment to or RNAPII and TFIIB occupancy of sn/snoRNA genes. Our analyses suggest that Mediator promotes PIC formation and transcription at sn/snoRNA genes, expanding the role of this critical regulator beyond its known functions in mRNA gene transcription and demonstrating further mechanistic similarity between the transcription of mRNA and sn/snoRNA genes. E ukaryotic RNA polymerase II (RNAPII), responsible for the transcription of mRNA genes, also transcribes several classes of non-protein-coding RNA (ncRNA) genes. Two prominent classes of RNAPII-transcribed eukaryotic ncRNA genes are small nuclear RNAs (snRNAs) and small nucleolar RNAs (snoRNAs). snRNAs are involved in pre-mRNA splicing (1), while snoRNAs primarily function in rRNA maturation via guiding methylation and pseudouridylation of specific rRNA bases (2).Most sn/snoRNA transcription in eukaryotes is carried out by RNAPII, with a few notable RNAPIII-transcribed exceptions, including the U6 snRNA gene (3). While transcription of both mRNA and the majority of sn/snoRNA genes is carried out by RNAPII, notable differences between their regulation have been described, particularly in metazoans. In addition to the documented dependence of a few sn/snoRNAs on several general transcription factors (GTFs) that are components of the preinitiation complex and generally essential for RNAPII transcription (TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and TFIIH) (4-6), metazoan sn/snoRNA gene transcription relies on a number of specialized factors. One such factor is the small nuclear RNA activating complex (SNAPc), which contains the TATA-binding protein (TBP) as well as five specific subunits and is essential for

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“…One possible mechanism for recruitment of Mediator to sn/snoRNAs is via the interaction of activators, including Tbf1, with other subunits of Mediator such as the tail/middle module connector Med16, which interacts with activators such as Gcn4 in yeast (45), DIF in Drosophila (50), and NRF2 in mouse and human (51). Indeed, a recent proteomic analysis of Mediator interactions reported a modest interaction between Mediator and Tbf1 (52). Mediator could also be recruited to sn/snoRNA genes independent of activators via interactions with the PIC (33, 53) (bioRxiv: https://doi.org/10.1101/207282).…”

Section: Discussionmentioning

confidence: 99%

Mediator is essential for small nuclear and nucleolar RNA transcription in yeast

Tourigny

Saleh

Zentner

2018

Preprint

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word count: 198 11 Introduction/results/discussion word count: 3,085 12 Materials and methods word count: 1,433 13 Abstract 14 Eukaryotic RNA polymerase II (RNAPII) transcribes mRNA genes as well as non-protein coding 15 RNAs (ncRNAs) including small nuclear and nucleolar RNAs (sn/snoRNAs). In metazoans, 16RNAPII transcription of sn/snoRNAs is facilitated by a number of specialized complexes, but no 17 such complexes have been discovered in yeast. It has thus been proposed that yeast 18 sn/snoRNA promoters use the same complement of factors as mRNA promoters, but the extent 19 to which key regulators of mRNA genes act at sn/snoRNA genes in yeast is unclear. Here, we 20 investigated a potential role for the Mediator complex, essential for mRNA gene transcription, in 21 the transcription of sn/snoRNA genes. We found that the complete Mediator complex maps to 22 most sn/snoRNA gene regulatory regions and that loss of Mediator function results in a robust 23 reduction in RNAPII and TFIIB occupancy at sn/snoRNA genes. Furthermore, deletion of 24 subunits of the activator-interacting Mediator tail module does not affect Mediator recruitment to, 25 or transcription of, sn/snoRNAs. Taken together, our analyses indicate that Mediator promotes 26 PIC formation and transcription at sn/snoRNA genes, expanding the role of this critical regulator 27 beyond its known functions in mRNA gene transcription and demonstrating further mechanistic 28 similarity between the transcription of mRNA and sn/snoRNA genes. 29

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Proteomic Analysis of the Mediator Complex Interactome in Saccharomyces cerevisiae

Cited by 24 publications

References 66 publications

PPARβ/δ controls Mediator recruitment and transcription initiation

PPARβ/δ controls Mediator recruitment and transcription initiation

Mediator Is Essential for Small Nuclear and Nucleolar RNA Transcription in Yeast

Mediator is essential for small nuclear and nucleolar RNA transcription in yeast

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