Gene Symbol: MED4
Description: Med4p
Alias: Med4p
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Koschubs T, Lorenzen K, Baumli S, Sandström S, Heck A, Cramer P. Preparation and topology of the Mediator middle module. Nucleic Acids Res. 2010;38:3186-95 pubmed publisher
    ..Protein-protein interaction assays combined with previously published data suggest that the Med7 and Med4 subunits serve as a binding platform to form the three heterodimeric subcomplexes, Med7N/21, Med7C/31 and Med4/9...
  2. Lorch Y, Beve J, Gustafsson C, Myers L, Kornberg R. Mediator-nucleosome interaction. Mol Cell. 2000;6:197-201 pubmed
    ..Sequence alignment shows significant similarity of Nut1 to the GCN5-related N-acetyltransferase superfamily. Finally, recombinant Nut1 exhibits HAT activity in an in-gel assay. ..
  3. Lariviere L, Seizl M, van Wageningen S, Röther S, van de Pasch L, Feldmann H, et al. Structure-system correlation identifies a gene regulatory Mediator submodule. Genes Dev. 2008;22:872-7 pubmed publisher
    ..The presented structure-based system perturbation is superior to gene deletion analysis of gene regulation. ..
  4. Myers L, Gustafsson C, Hayashibara K, Brown P, Kornberg R. Mediator protein mutations that selectively abolish activated transcription. Proc Natl Acad Sci U S A. 1999;96:67-72 pubmed
    ..These findings make an important connection between transcriptional activation in vitro and in vivo, and identify Mediator as a "global" transcriptional coactivator. ..
  5. Linder T, Zhu X, Baraznenok V, Gustafsson C. The classical srb4-138 mutant allele causes dissociation of yeast Mediator. Biochem Biophys Res Commun. 2006;349:948-53 pubmed
    ..Interestingly, both sub-complexes are able to associate with an active promoter at the permissive temperature but at the non-permissive temperature the head domain is lost from the promoter. ..
  6. Lee Y, Park J, Min S, Han S, Kim Y. An activator binding module of yeast RNA polymerase II holoenzyme. Mol Cell Biol. 1999;19:2967-76 pubmed
  7. Baumli S, Hoeppner S, Cramer P. A conserved mediator hinge revealed in the structure of the MED7.MED21 (Med7.Srb7) heterodimer. J Biol Chem. 2005;280:18171-8 pubmed
    ..MED21 hinge could account for changes in overall Mediator structure upon binding to Pol II or activators. Our results support the idea that transcription regulation involves conformational changes within the general machinery. ..
  8. Cai G, Imasaki T, Takagi Y, Asturias F. Mediator structural conservation and implications for the regulation mechanism. Structure. 2009;17:559-67 pubmed publisher
    ..This suggests that the topology and structural dynamics of Mediator constitute important elements of a conserved regulation mechanism. ..
  9. Takahashi H, Kasahara K, Kokubo T. Saccharomyces cerevisiae Med9 comprises two functionally distinct domains that play different roles in transcriptional regulation. Genes Cells. 2009;14:53-67 pubmed publisher
    ..half (aa 64-149) has a more fundamental function involved in direct binding to the amino-terminal portions of Med4 and Med7 and the assembly of Med9 into the Middle module...

More Information


  1. Han S, Lee J, Kang J, Kim Y. Med9/Cse2 and Gal11 modules are required for transcriptional repression of distinct group of genes. J Biol Chem. 2001;276:37020-6 pubmed
  2. Myers L, Gustafsson C, Bushnell D, Lui M, Erdjument Bromage H, Tempst P, et al. The Med proteins of yeast and their function through the RNA polymerase II carboxy-terminal domain. Genes Dev. 1998;12:45-54 pubmed
    ..Evidence for human homologs of several mediator proteins, including Med7, points to similar mechanisms in higher cells. ..
  3. Han S, Lee Y, Gim B, Ryu G, Park S, Lane W, et al. Activator-specific requirement of yeast mediator proteins for RNA polymerase II transcriptional activation. Mol Cell Biol. 1999;19:979-88 pubmed
  4. Baidoobonso S, Guidi B, Myers L. Med19(Rox3) regulates Intermodule interactions in the Saccharomyces cerevisiae mediator complex. J Biol Chem. 2007;282:5551-9 pubmed
    ..Although the Middle module is unnecessary for holding the Head and Tail modules together, it is required for the complex to function as a conduit between activators and the core transcription machinery. ..
  5. Seizl M, Lariviere L, Pfaffeneder T, Wenzeck L, Cramer P. Mediator head subcomplex Med11/22 contains a common helix bundle building block with a specific function in transcription initiation complex stabilization. Nucleic Acids Res. 2011;39:6291-304 pubmed publisher
    ..also present in the Mediator middle module subcomplex Med7/21 and is predicted in the Mediator heterodimers Med2/3, Med4/9, Med10/14 and Med28/30...
  6. 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;20:8709-19 pubmed
  7. Eyboulet F, Wydau Dematteis S, Eychenne T, Alibert O, Neil H, Boschiero C, et al. Mediator independently orchestrates multiple steps of preinitiation complex assembly in vivo. Nucleic Acids Res. 2015;43:9214-31 pubmed publisher
    ..This study provides an extensive genome-wide view of Mediator's role in PIC formation, suggesting that Mediator coordinates multiple steps of a PIC assembly pathway. ..
  8. Balciunas D, Gälman C, Ronne H, Bjorklund S. The Med1 subunit of the yeast mediator complex is involved in both transcriptional activation and repression. Proc Natl Acad Sci U S A. 1999;96:376-81 pubmed
    ..Finally, we show that the Med2 protein is lost from the mediator on purification from Med1-deficient cells, indicating a physical interaction between Med1 and Med2. ..
  9. Gustafsson C, Myers L, Beve J, Spahr H, Lui M, Erdjument Bromage H, et al. Identification of new mediator subunits in the RNA polymerase II holoenzyme from Saccharomyces cerevisiae. J Biol Chem. 1998;273:30851-4 pubmed
    ..MED11 is a previously uncharacterized gene. The existence of these proteins in the mediator complex was verified by copurification and co-immunoprecipitation with RNA polymerase II holoenzyme. ..
  10. Kim S, Gross D. Mediator recruitment to heat shock genes requires dual Hsf1 activation domains and mediator tail subunits Med15 and Med16. J Biol Chem. 2013;288:12197-213 pubmed publisher
  11. Balciunas D, Hallberg M, Bjorklund S, Ronne H. Functional interactions within yeast mediator and evidence of differential subunit modifications. J Biol Chem. 2003;278:3831-9 pubmed
    ..Both lexA-Med1 and lexA-Srb7 are stably associated with Med4 and Med8, which suggests that they are incorporated into Mediator...
  12. Papamichos Chronakis M, Conlan R, Gounalaki N, Copf T, Tzamarias D. Hrs1/Med3 is a Cyc8-Tup1 corepressor target in the RNA polymerase II holoenzyme. J Biol Chem. 2000;275:8397-403 pubmed
  13. Liu Y, Kung C, Fishburn J, Ansari A, Shokat K, Hahn S. Two cyclin-dependent kinases promote RNA polymerase II transcription and formation of the scaffold complex. Mol Cell Biol. 2004;24:1721-35 pubmed
    ..In addition to the previously known substrate, the Pol II CTD, it was found that Kin28 phosphorylates two subunits of Mediator and Srb10 targets two subunits of TFIID for phosphorylation. ..
  14. Eychenne T, Novikova E, Barrault M, Alibert O, Boschiero C, Peixeiro N, et al. Functional interplay between Mediator and TFIIB in preinitiation complex assembly in relation to promoter architecture. Genes Dev. 2016;30:2119-2132 pubmed
    ..This study thus provides mechanistic insights into the coordinated function of Mediator and TFIIB in PIC assembly in different chromatin contexts. ..
  15. Liu Z, Myers L. Med5(Nut1) and Med17(Srb4) are direct targets of mediator histone H4 tail interactions. PLoS ONE. 2012;7:e38416 pubmed publisher
    ..This analysis has identified the Med5 subunit of Mediator as a target for histone tail interactions and suggests that the previously observed effect of med5 mutations on telomeric heterochromatin and silencing is direct. ..
  16. Lee Y, Kim Y. Requirement for a functional interaction between mediator components Med6 and Srb4 in RNA polymerase II transcription. Mol Cell Biol. 1998;18:5364-70 pubmed
    ..Our results suggest not only the existence of a specific interaction between Med6 and Srb4 but also the requirement of this interaction in transcriptional regulation of RNA polymerase II holoenzyme. ..
  17. Miller C, Matic I, Maier K, Schwalb B, Roether S, Strasser K, et al. Mediator phosphorylation prevents stress response transcription during non-stress conditions. J Biol Chem. 2012;287:44017-26 pubmed publisher
    ..Thus dynamic and differential Mediator phosphorylation contributes to gene regulation in eukaryotic cells. ..
  18. Guidi B, Bjornsdottir G, Hopkins D, Lacomis L, Erdjument Bromage H, Tempst P, et al. Mutual targeting of mediator and the TFIIH kinase Kin28. J Biol Chem. 2004;279:29114-20 pubmed
    ..In addition, we have found that Kin28 phosphorylates Mediator subunit Med4 in an assay, including purified holo-TFIIH, and either Mediator or recombinant Med4 alone...
  19. Hallberg M, Hu G, Tronnersjö S, Shaikhibrahim Z, Balciunas D, Bjorklund S, et al. Functional and physical interactions within the middle domain of the yeast mediator. Mol Genet Genomics. 2006;276:197-210 pubmed
    ..2-Hybrid experiments confirmed multiple interactions between Med21, Med10, Med7 and Med4, and also revealed a Med21 self-interaction...