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

Ansari, Suraiya A.; Paul, Emily; Sommer, Sebastian; Lieleg, Corinna; He, Qiye; Daly, Alexandre Z.; Rode, Kara A.; Barber, Wesley T.; Ellis, Laura; LaPorta, Erika; Orzechowski, Amanda M.; Taylor, Emily J. A.; Reeb, Tanner; Wong, Jason P.; Korber, Philipp; Morse, Randall H.

doi:10.1074/jbc.m113.529354

Cited by 26 publications

(22 citation statements)

References 75 publications

(121 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This idea is supported by studies of S. cerevisiae showing the occupancy of the SAGA coactivator complex at certain promoters can be interdependent with (14) or dependent on (13) Mediator and its tail module subunits. A recent study shows that Swi/Snf activity at the S. cerevisiae CHA1 promoter also is dependent on Mediator tail module subunits (45). Consistent with such a scenario, we have found that the TADs of ScMed2 and ScMed3 appear to function redundantly in the induction of high levels of activated transcription.…”

Section: Resultssupporting

confidence: 72%

“…The S. cerevisiae Mediator tail module largely regulates SAGA-dependent genes and helps direct the activity of the SAGA and Swi/Snf coactivator complexes to specific promoters (13,14,45,47). The interaction of Mediator-associated activation domains with wellcharacterized targets of certain DNA-bound transcriptional activators (1), such as Tra1 (48), could explain how Mediator coordinates the recruitment of SAGA or other coactivators.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Fungal Mediator Tail Subunits Contain Classical Transcriptional Activation Domains

Liu

Myers

2015

Molecular and Cellular Biology

View full text Add to dashboard Cite

Classical activation domains within DNA-bound eukaryotic transcription factors make weak interactions with coactivator complexes, such as Mediator, to stimulate transcription. How these interactions stimulate transcription, however, is unknown. The activation of reporter genes by artificial fusion of Mediator subunits to DNA binding domains that bind to their promoters has been cited as evidence that the primary role of activators is simply to recruit Mediator. We have identified potent classical transcriptional activation domains in the C termini of several tail module subunits of Saccharomyces cerevisiae, Candida albicans, and Candida dubliniensis Mediator, while their N-terminal domains are necessary and sufficient for their incorporation into Mediator but do not possess the ability to activate transcription when fused to a DNA binding domain. This suggests that Mediator fusion proteins actually are functioning in a manner similar to that of a classical DNA-bound activator rather than just recruiting Mediator. Our finding that deletion of the activation domains of S. cerevisiae Med2 and Med3, as well as C. dubliniensis Tlo1 (a Med2 ortholog), impairs the induction of certain genes shows these domains function at native promoters. Activation domains within coactivators are likely an important feature of these complexes and one that may have been uniquely leveraged by a common fungal pathogen.

show abstract

Section: Resultssupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Fungal Mediator Tail Subunits Contain Classical Transcriptional Activation Domains

Liu

Myers

2015

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

“…This double mutant was previously shown to lead to a loss of Tail module functions (Ansari et al, 2012, 2014; Paul et al, 2015; Zhang et al, 2004), so we will refer to these cells (med3Δ/med15Δ) as TailΔ. Very strikingly, Mediator occupancy at UAS regions was reduced to background level in TailΔ cells (Figures 3A and 3B, KIN28 WT).…”

Section: Resultsmentioning

confidence: 93%

Tail and Kinase Modules Differently Regulate Core Mediator Recruitment and Function In Vivo

et al. 2016

View full text Add to dashboard Cite

Summary Mediator is a highly conserved transcriptional coactivator organized into four modules, namely Tail, Middle, Head, and Kinase (CKM). Previous work suggests regulatory roles for Tail and CKM, but an integrated model for these activities is lacking. Here, we analyzed the genome-wide distribution of Mediator subunits in wild-type and mutant yeast cells in which RNA polymerase II promoter escape is blocked, allowing detection of transient Mediator forms. We found that although all modules are recruited to upstream activated regions (UAS), assembly of Mediator within the pre-initiation complex is accompanied by the release of CKM. Interestingly, our data show that CKM regulates Mediator-UAS interaction rather than Mediator-promoter association. In addition, although Tail is required for Mediator recruitment to UAS, Tailless Mediator nevertheless interacts with core promoters. Collectively, our data suggest that the essential function of Mediator is mediated by Head and Middle at core promoters, while Tail and CKM play regulatory roles.

show abstract

“…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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

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

Cited by 26 publications

References 75 publications

Fungal Mediator Tail Subunits Contain Classical Transcriptional Activation Domains

Fungal Mediator Tail Subunits Contain Classical Transcriptional Activation Domains

Tail and Kinase Modules Differently Regulate Core Mediator Recruitment and Function In Vivo

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

Contact Info

Product

Resources

About