Gene Symbol: SIN4
Description: Sin4p
Alias: BEL2, GAL22, MED16, RYE1, SDI3, SSF5, SSN4, SSX3, TSF3, Sin4p
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Li L, Quinton T, Miles S, Breeden L. Genetic interactions between mediator and the late G1-specific transcription factor Swi6 in Saccharomyces cerevisiae. Genetics. 2005;171:477-88 pubmed
    ..Mutations in tail module components sin4 and pgd1 showed both growth defects and suppression when combined with swi6, but a third tail component, gal11, ..
  2. 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. ..
  3. 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. ..
  4. 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. ..
  5. 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. ..
  6. Howard S, Chang Y, Budovskaya Y, Herman P. The Ras/PKA signaling pathway of Saccharomyces cerevisiae exhibits a functional interaction with the Sin4p complex of the RNA polymerase II holoenzyme. Genetics. 2001;159:77-89 pubmed
    ..Moreover, mutations that affected proteins within the Sin4p module of the Mediator exhibited specific genetic interactions with the Ras protein signaling pathway...
  7. 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
  8. 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
  9. Yu Y, Eriksson P, Stillman D. Architectural transcription factors and the SAGA complex function in parallel pathways to activate transcription. Mol Cell Biol. 2000;20:2350-7 pubmed
    ..performed a functional analysis of HO regulation by determining the ability of mutations in SIN1, SIN3, RPD3, and SIN4 negative regulators to permit HO expression in the absence of certain activators...

More Information


  1. Singh H, Erkine A, Kremer S, Duttweiler H, Davis D, Iqbal J, et al. A functional module of yeast mediator that governs the dynamic range of heat-shock gene expression. Genetics. 2006;172:2169-84 pubmed
    ..the six subunits, Med7, Med10/Nut2, and Med21/Srb7, map to Mediator's middle domain; two subunits, Med14/Rgr1 and Med16/Sin4, to its tail domain; and one subunit, Med19/Rox3, to its head domain...
  2. Li Y, Bjorklund S, Jiang Y, Kim Y, Lane W, Stillman D, et al. Yeast global transcriptional regulators Sin4 and Rgr1 are components of mediator complex/RNA polymerase II holoenzyme. Proc Natl Acad Sci U S A. 1995;92:10864-8 pubmed
    b>Sin4 and Rgr1 proteins, previously shown by genetic studies to play both positive and negative roles in the transcriptional regulation of many genes, are identified here as components of mediator and RNA polymerase II holoenzyme complexes...
  3. 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. ..
  4. Wang X, Michels C. Mutations in SIN4 and RGR1 cause constitutive expression of MAL structural genes in Saccharomyces cerevisiae. Genetics. 2004;168:747-57 pubmed
    ..1 and group 2 mutants exhibit pleiotropic phenotypes and represent alleles of Mediator component genes RGR1 and SIN4, respectively...
  5. Jiang Y, Dohrmann P, Stillman D. Genetic and physical interactions between yeast RGR1 and SIN4 in chromatin organization and transcriptional regulation. Genetics. 1995;140:47-54 pubmed
    ..Finally, we use yeast strains expressing GST fusion proteins to demonstrate that the Sin4p and Rgr1p proteins are physically associated in vivo...
  6. Stillman D, Dorland S, Yu Y. Epistasis analysis of suppressor mutations that allow HO expression in the absence of the yeast SW15 transcriptional activator. Genetics. 1994;136:781-8 pubmed
    ..We show that the RPD3 gene is the same as SDI2, and that SIN4 is the same as the TSF3 and SDI3 genes. We have also identified a new swi5 suppressor, RGR1...
  7. Nishizawa M. Negative regulation of transcription by the yeast global transcription factors, Gal11 and Sin4. Yeast. 2001;18:1099-110 pubmed
    Gal11 and Sin4 proteins are yeast global transcription factors that regulate transcription of a variety of genes, both positively and negatively...
  8. Kim D, Kim G, Yun C, Lee Y. Functional conservation of the glutamine-rich domains of yeast Gal11 and human SRC-1 in the transactivation of glucocorticoid receptor Tau 1 in Saccharomyces cerevisiae. Mol Cell Biol. 2008;28:913-25 pubmed
    ..These results suggest that there is functional conservation between Qr domains of yeast Gal11p and mammalian SRC proteins as direct targets of activator proteins in yeast. ..
  9. Roberts S, Winston F. Essential functional interactions of SAGA, a Saccharomyces cerevisiae complex of Spt, Ada, and Gcn5 proteins, with the Snf/Swi and Srb/mediator complexes. Genetics. 1997;147:451-65 pubmed
    ..Our screen identified mutations in SNF2, SIN4, and GAL11...
  10. Fleckenstein A, Shallom J, Golin J. A PDR5-independent pathway of multi-drug resistance regulated by the SIN4 gene product. Yeast. 1999;15:133-7 pubmed
    The SIN4 locus encodes a global transcriptional regulator of various yeast genes...
  11. Lycan D, Mikesell G, Bunger M, Breeden L. Differential effects of Cdc68 on cell cycle-regulated promoters in Saccharomyces cerevisiae. Mol Cell Biol. 1994;14:7455-65 pubmed
    ..SSF5 is allelic with SIN4 (TSF3), a gene implicated in global repression of transcription and chromatin structure, and SSF9 is likely to be a ..
  12. Malagon F, Tong A, Shafer B, Strathern J. Genetic interactions of DST1 in Saccharomyces cerevisiae suggest a role of TFIIS in the initiation-elongation transition. Genetics. 2004;166:1215-27 pubmed
    ..copies of TAF14, SUA7, GAL11, RTS1, and TYS1 alleviate the growth phenotype of dst1 soh1 mutants; and (5) SRB5 and SIN4 genetically interact with DST1...
  13. Grandin N, Corset L, Charbonneau M. Genetic and physical interactions between Tel2 and the Med15 Mediator subunit in Saccharomyces cerevisiae. PLoS ONE. 2012;7:e30451 pubmed publisher
    ..Altogether, the present data suggest the existence of a novel role for Tel2, namely in transcription, possibly in cooperation with Rvb2 and involving the existence of physical interactions with the Med15/Gal11 Mediator subunit. ..
  14. Sakurai H, Fukasawa T. Artificial recruitment of certain Mediator components affects requirement of basal transcription factor IIE. Genes Cells. 2003;8:41-50 pubmed
    ..Our results strongly suggest that the TFIIE requirement of a gene is determined by a target(s) in Mediator through which the signal of the cognate activator is transmitted. ..
  15. Dettmann A, Jäschke Y, Triebel I, Bogs J, Schröder I, Schüller H. Mediator subunits and histone methyltransferase Set2 contribute to Ino2-dependent transcriptional activation of phospholipid biosynthesis in the yeast Saccharomyces cerevisiae. Mol Genet Genomics. 2010;283:211-21 pubmed publisher
    ..In contrast, Ino2 directly binds to the Set2 histone methyltransferase. Mapping of interaction domains revealed the importance of the SET core domain which was necessary and sufficient for binding Ino2. ..
  16. Ratnakumar S, Young E. Snf1 dependence of peroxisomal gene expression is mediated by Adr1. J Biol Chem. 2010;285:10703-14 pubmed publisher
  17. Alepuz P, de Nadal E, Zapater M, Ammerer G, Posas F. Osmostress-induced transcription by Hot1 depends on a Hog1-mediated recruitment of the RNA Pol II. EMBO J. 2003;22:2433-42 pubmed
    ..The mammalian p38 also interacts with the RNA Pol II, which might suggest a conserved mechanism for regulation of gene expression by SAPKs among eukaryotic cells. ..
  18. Reeves W, Hahn S. Activator-independent functions of the yeast mediator sin4 complex in preinitiation complex formation and transcription reinitiation. Mol Cell Biol. 2003;23:349-58 pubmed
    ..Previously, subunits of the Sin4 Mediator complex (Sin4, Pgd1, Gal11, and Med2) have been implicated in both positive and negative transcriptional ..
  19. Valay J, Simon M, Dubois M, Bensaude O, Facca C, Faye G. The KIN28 gene is required both for RNA polymerase II mediated transcription and phosphorylation of the Rpb1p CTD. J Mol Biol. 1995;249:535-44 pubmed
    ..a kin28 thermosensitive mutation (kin28-ts3) has uncovered genetic interactions between gene KIN28 and genes RAD3, SIN4, STI1 and CDC37...
  20. 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. ..
  21. 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
    ..The subunits, Med1 and Med10, which bridge to the Mediator tail module, bind to both Med7 and Med4. ..
  22. Lee Y, Min S, Gim B, Kim Y. A transcriptional mediator protein that is required for activation of many RNA polymerase II promoters and is conserved from yeast to humans. Mol Cell Biol. 1997;17:4622-32 pubmed
    ..A database search revealed the existence of MED6-related genes in humans and Caenorhabditis elegans, suggesting that the role of mediator in transcriptional activation is conserved throughout the evolution. ..
  23. Howard S, Budovskaya Y, Chang Y, Herman P. The C-terminal domain of the largest subunit of RNA polymerase II is required for stationary phase entry and functionally interacts with the Ras/PKA signaling pathway. J Biol Chem. 2002;277:19488-97 pubmed
    ..In all, these data suggested that S. cerevisiae growth control and RNA pol II transcription might be coupled by using the Ras pathway to regulate CTD function. ..
  24. 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
    ..Likewise, ablation of either of two Mediator Tail subunits, Med15 or Med16, reduces Mediator recruitment to HSP promoters, whereas deletion of both abolishes it...
  25. Wahba L, Amon J, Koshland D, Vuica Ross M. RNase H and multiple RNA biogenesis factors cooperate to prevent RNA:DNA hybrids from generating genome instability. Mol Cell. 2011;44:978-88 pubmed publisher
    ..In summary, RNA:DNA hybrids are a potent source for changing genome structure. By preventing their formation and accumulation, multiple RNA biogenesis factors and RNase H act as guardians of the genome. ..
  26. Yu Y, Jiang Y, Wellinger R, Carlson K, Roberts J, Stillman D. Mutations in the homologous ZDS1 and ZDS2 genes affect cell cycle progression. Mol Cell Biol. 1996;16:5254-63 pubmed
    ..A zds1 deletion exhibits genetic interactions with cdc28-1N but not with other cdc28 alleles. SIN4 encodes a protein which is part of the RNA polymerase II holoenzyme-mediator complex, and a sin4 null mutation has ..
  27. Valencia Burton M, Oki M, Johnson J, Seier T, Kamakaka R, Haber J. Different mating-type-regulated genes affect the DNA repair defects of Saccharomyces RAD51, RAD52 and RAD55 mutants. Genetics. 2006;174:41-55 pubmed
    ..rad51-K191R is uniquely suppressed by deleting the RME1 gene encoding a repressor of meiosis or its coregulator SIN4; this effect is independent of the meiosis-specific homolog, Dmc1...
  28. 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
  29. West R, Kruger B, Thomas S, Ma J, Milgrom E. RLR1 (THO2), required for expressing lacZ fusions in yeast, is conserved from yeast to humans and is a suppressor of SIN4. Gene. 2000;243:195-205 pubmed
    ..a mutation (rlr1-1; required for lacZ RNA) in the Saccharomyces cerevisiae (Sc) RLR1 gene as a suppressor of sin4, a component of the Mediator subcomplex of the RNA polymerase II holoenzyme and a determinant of chromatin ..
  30. van Heusden G, Steensma H. 14-3-3 Proteins are essential for regulation of RTG3-dependent transcription in Saccharomyces cerevisiae. Yeast. 2001;18:1479-91 pubmed
    ..In this study we constructed a mutant with a single, temperature-sensitive bmh allele. Recessive mutations in SIN4 and RTG3 can suppress the temperature-sensitive phenotype of this mutant...
  31. Chang M, French Cornay D, Fan H, Klein H, Denis C, Jaehning J. A complex containing RNA polymerase II, Paf1p, Cdc73p, Hpr1p, and Ccr4p plays a role in protein kinase C signaling. Mol Cell Biol. 1999;19:1056-67 pubmed
    ..Our observation that the Mpk1p kinase is fully active in a paf1Delta strain indicates that the Paf1p-Cdc73p complex may function downstream of the Pkc1p-Mpk1p cascade to regulate the expression of a subset of yeast genes. ..
  32. Song W, Carlson M. Srb/mediator proteins interact functionally and physically with transcriptional repressor Sfl1. EMBO J. 1998;17:5757-65 pubmed
    ..We show here that the defect in repression of SUC2 caused by mutation of SRB8, SRB9, SRB11, SIN4 or ROX3 is suppressed by increased dosage of the SFL1 gene, and the genetic behavior of the sfl1Delta mutation ..
  33. Peiró Chova L, Estruch F. Specific defects in different transcription complexes compensate for the requirement of the negative cofactor 2 repressor in Saccharomyces cerevisiae. Genetics. 2007;176:125-38 pubmed
  34. Carlson M, Osmond B, Neigeborn L, Botstein D. A suppressor of SNF1 mutations causes constitutive high-level invertase synthesis in yeast. Genetics. 1984;107:19-32 pubmed
    ..Genetic analysis suggested that the ssn6 mutations are allelic to the cyc8 mutation isolated by R. J. Rothstein and F. Sherman, which causes increased production of iso-2-cytochrome c. The data suggest a regulatory function for SSN6 . ..
  35. 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. ..
  36. Kim S, Cabane K, Hampsey M, Reinberg D. Genetic analysis of the YDR1-BUR6 repressor complex reveals an intricate balance among transcriptional regulatory proteins in yeast. Mol Cell Biol. 2000;20:2455-65 pubmed
    ..suppressors of a cold-sensitive ydr1 (ydr1(cs)) mutant led to the identification of recessive mutations in the SIN4 gene, which encodes a component of the SRB-MED complex...
  37. Schroder M, Clark R, Kaufman R. IRE1- and HAC1-independent transcriptional regulation in the unfolded protein response of yeast. Mol Microbiol. 2003;49:591-606 pubmed
    ..A genetic screen identified recessive SIN4 alleles as suppressors of a defective UPR in ire1 Delta strains...
  38. Piruat J, Chavez S, Aguilera A. The yeast HRS1 gene is involved in positive and negative regulation of transcription and shows genetic characteristics similar to SIN4 and GAL11. Genetics. 1997;147:1585-94 pubmed
    ..Many of these phenotypes also result from mutations in GAL11, SIN4 or RGR1, which encode proteins of the RNA polII mediator...
  39. Jedidi I, Zhang F, Qiu H, Stahl S, Palmer I, Kaufman J, et al. Activator Gcn4 employs multiple segments of Med15/Gal11, including the KIX domain, to recruit mediator to target genes in vivo. J Biol Chem. 2010;285:2438-55 pubmed publisher
    ..Gcn4 is distinctive in relying on comparable contributions from multiple segments of Gal11 for efficient recruitment of Mediator in vivo. ..
  40. Kuchin S, Treich I, Carlson M. A regulatory shortcut between the Snf1 protein kinase and RNA polymerase II holoenzyme. Proc Natl Acad Sci U S A. 2000;97:7916-20 pubmed
    ..These results suggest that direct regulatory interactions between signal transduction pathways and RNA polymerase II holoenzyme provide a mechanism for transcriptional control in response to important signals. ..
  41. Herbig E, Warfield L, Fish L, Fishburn J, Knutson B, Moorefield B, et al. Mechanism of Mediator recruitment by tandem Gcn4 activation domains and three Gal11 activator-binding domains. Mol Cell Biol. 2010;30:2376-90 pubmed publisher
    ..The Gcn4 N-terminal activation domain also cross-links to the Mediator subunit Sin4/Med16. The contribution of the two Gcn4 activation domains to transcription was gene specific and varied from ..
  42. 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. ..
  43. Tabtiang R, Herskowitz I. Nuclear proteins Nut1p and Nut2p cooperate to negatively regulate a Swi4p-dependent lacZ reporter gene in Saccharomyces cerevisiae. Mol Cell Biol. 1998;18:4707-18 pubmed
    ..These results suggest that Nut1p, Nut2p, Sin4p, and Ccr4p define a group of proteins that negatively regulate transcription in a subtle manner which is revealed ..
  44. Galdieri L, Desai P, Vancura A. Facilitated assembly of the preinitiation complex by separated tail and head/middle modules of the mediator. J Mol Biol. 2012;415:464-74 pubmed publisher
    ..Deletion of one of the tail subunits SIN4 results in derepression of a subset of genes, including FLR1, by a largely unknown mechanism...
  45. Cai G, Imasaki T, Yamada K, Cardelli F, Takagi Y, Asturias F. Mediator head module structure and functional interactions. Nat Struct Mol Biol. 2010;17:273-9 pubmed publisher
  46. 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. ..
  47. Romero C, Desai P, DeLillo N, Vancura A. Expression of FLR1 transporter requires phospholipase C and is repressed by Mediator. J Biol Chem. 2006;281:5677-85 pubmed
    ..However, our screen identified SIN4, encoding a component of the Mediator complex of RNA polymerase II...
  48. Mizuno T, Harashima S. Gal11 is a general activator of basal transcription, whose activity is regulated by the general repressor Sin4 in yeast. Mol Genet Genomics. 2003;269:68-77 pubmed
    Mutations in SIN4, which encodes a global transcriptional regulator in Saccharomyces cerevisiae, have been suggested to lead to an increase in basal transcription of various genes by causing an alteration in chromatin structure...
  49. 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. ..
  50. 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
    ..such fusions of the lexA DNA binding domain to Med1, Med2, Gal11, Srb7, and Srb10 in wild type, med1, med2, gal11, sin4, srb8, srb10, and srb11 strains...