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

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2016 Nov 5

PMID 27773677

Citations 75

Authors

Celia Jeronimo

Marie-France Langelier

Alain R Bataille

John M Pascal

B Franklin Pugh

Francois Robert

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Mechanisms of synergistic Mediator recruitment in RNA polymerase II transcription activation revealed by single-molecule fluorescence.

Zhou D, Jeon J, Farheen N, Friedman L, Kondev J, Buratowski S bioRxiv. 2024; .

PMID: 39713438 PMC: 11661148. DOI: 10.1101/2024.12.10.627625.

The CDK8 kinase module: A novel player in the transcription of translation initiation and ribosomal genes.

Friedson B, Willis S, Shcherbik N, Campbell A, Cooper K Mol Biol Cell. 2024; 36(1):ar2.

PMID: 39565680 PMC: 11742111. DOI: 10.1091/mbc.E24-04-0164.

Revisiting the model for coactivator recruitment: Med15 can select its target sites independent of promoter-bound transcription factors.

Mindel V, Brodsky S, Yung H, Manadre W, Barkai N Nucleic Acids Res. 2024; 52(20):12093-12111.

PMID: 39187372 PMC: 11551773. DOI: 10.1093/nar/gkae718.

Structures and compositional dynamics of Mediator in transcription regulation.

Li T, Chao T, Tsai K Curr Opin Struct Biol. 2024; 88:102892.

PMID: 39067114 PMC: 11779508. DOI: 10.1016/j.sbi.2024.102892.

An IDR-dependent mechanism for nuclear receptor control of Mediator interaction with RNA polymerase II.

Zhao H, Li J, Xiang Y, Malik S, Vartak S, Veronezi G Mol Cell. 2024; 84(14):2648-2664.e10.

PMID: 38955181 PMC: 11283359. DOI: 10.1016/j.molcel.2024.06.006.

References

Li Y, Bjorklund S, Jiang Y, Kim Y, Lane W, Stillman D . Yeast global transcriptional regulators Sin4 and Rgr1 are components of mediator complex/RNA polymerase II holoenzyme. Proc Natl Acad Sci U S A. 1995; 92(24):10864-8. PMC: 40531. DOI: 10.1073/pnas.92.24.10864. View

Levine M, Cattoglio C, Tjian R . Looping back to leap forward: transcription enters a new era. Cell. 2014; 157(1):13-25. PMC: 4059561. DOI: 10.1016/j.cell.2014.02.009. View

Stevens J, Cantin G, Wang G, Shevchenko A, Shevchenko A, Berk A . Transcription control by E1A and MAP kinase pathway via Sur2 mediator subunit. Science. 2002; 296(5568):755-8. DOI: 10.1126/science.1068943. View

Herbig E, Warfield L, Fish L, Fishburn J, Knutson B, Moorefield B . Mechanism of Mediator recruitment by tandem Gcn4 activation domains and three Gal11 activator-binding domains. Mol Cell Biol. 2010; 30(10):2376-90. PMC: 2863704. DOI: 10.1128/MCB.01046-09. View

Fryer C, White J, Jones K . Mastermind recruits CycC:CDK8 to phosphorylate the Notch ICD and coordinate activation with turnover. Mol Cell. 2004; 16(4):509-20. DOI: 10.1016/j.molcel.2004.10.014. View

Brunelle M, Coulombe C, Poitras C, Robert M, Markovits A, Robert F . Aggregate and Heatmap Representations of Genome-Wide Localization Data Using VAP, a Versatile Aggregate Profiler. Methods Mol Biol. 2015; 1334:273-98. DOI: 10.1007/978-1-4939-2877-4_18. View

Dotson M, Yuan C, Roeder R, Myers L, Gustafsson C, Jiang Y . Structural organization of yeast and mammalian mediator complexes. Proc Natl Acad Sci U S A. 2000; 97(26):14307-10. PMC: 18914. DOI: 10.1073/pnas.260489497. View

Malik S, Roeder R . The metazoan Mediator co-activator complex as an integrative hub for transcriptional regulation. Nat Rev Genet. 2010; 11(11):761-72. PMC: 3217725. DOI: 10.1038/nrg2901. View

Naar A, Taatjes D, Zhai W, Nogales E, Tjian R . Human CRSP interacts with RNA polymerase II CTD and adopts a specific CTD-bound conformation. Genes Dev. 2002; 16(11):1339-44. PMC: 186316. DOI: 10.1101/gad.987602. View

10.

Plaschka C, Lariviere L, Wenzeck L, Seizl M, Hemann M, Tegunov D . Architecture of the RNA polymerase II-Mediator core initiation complex. Nature. 2015; 518(7539):376-80. DOI: 10.1038/nature14229. View

11.

Nelson C, Goto S, Lund K, Hung W, Sadowski I . Srb10/Cdk8 regulates yeast filamentous growth by phosphorylating the transcription factor Ste12. Nature. 2003; 421(6919):187-90. DOI: 10.1038/nature01243. View

12.

Wang G, Balamotis M, Stevens J, Yamaguchi Y, Handa H, Berk A . Mediator requirement for both recruitment and postrecruitment steps in transcription initiation. Mol Cell. 2005; 17(5):683-94. DOI: 10.1016/j.molcel.2005.02.010. View

13.

Holstege F, Jennings E, Wyrick J, Lee T, Hengartner C, Green M . Dissecting the regulatory circuitry of a eukaryotic genome. Cell. 1998; 95(5):717-28. DOI: 10.1016/s0092-8674(00)81641-4. View

14.

Raithatha S, Su T, Lourenco P, Goto S, Sadowski I . Cdk8 regulates stability of the transcription factor Phd1 to control pseudohyphal differentiation of Saccharomyces cerevisiae. Mol Cell Biol. 2011; 32(3):664-74. PMC: 3266601. DOI: 10.1128/MCB.05420-11. View

15.

Zhu X, Wiren M, Sinha I, Rasmussen N, Linder T, Holmberg S . Genome-wide occupancy profile of mediator and the Srb8-11 module reveals interactions with coding regions. Mol Cell. 2006; 22(2):169-78. DOI: 10.1016/j.molcel.2006.03.032. View

16.

Poss Z, Ebmeier C, Odell A, Tangpeerachaikul A, Lee T, Pelish H . Identification of Mediator Kinase Substrates in Human Cells using Cortistatin A and Quantitative Phosphoproteomics. Cell Rep. 2016; 15(2):436-50. PMC: 4833653. DOI: 10.1016/j.celrep.2016.03.030. View

17.

Davis M, Larimore E, Fissel B, Swanger J, Taatjes D, Clurman B . The SCF-Fbw7 ubiquitin ligase degrades MED13 and MED13L and regulates CDK8 module association with Mediator. Genes Dev. 2013; 27(2):151-6. PMC: 3566307. DOI: 10.1101/gad.207720.112. View

18.

Park J, Kim H, Han S, Hwang M, Lee Y, Kim Y . In vivo requirement of activator-specific binding targets of mediator. Mol Cell Biol. 2000; 20(23):8709-19. PMC: 86488. DOI: 10.1128/MCB.20.23.8709-8719.2000. View

19.

Wang X, Sun Q, Ding Z, Ji J, Wang J, Kong X . Redefining the modular organization of the core Mediator complex. Cell Res. 2014; 24(7):796-808. PMC: 4085763. DOI: 10.1038/cr.2014.64. View

20.

Jeronimo C, Watanabe S, Kaplan C, Peterson C, Robert F . The Histone Chaperones FACT and Spt6 Restrict H2A.Z from Intragenic Locations. Mol Cell. 2015; 58(6):1113-23. PMC: 4475440. DOI: 10.1016/j.molcel.2015.03.030. View