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SIN4  -  Sin4p

Saccharomyces cerevisiae S288c

Synonyms: BEL2, GAL22, Global transcriptional regulator SIN4, MED16, Mediator complex subunit 16, ...
 
 
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Disease relevance of SIN4

 

High impact information on SIN4

  • Yeast global transcriptional regulators Sin4 and Rgr1 are components of mediator complex/RNA polymerase II holoenzyme [2].
  • Each of these proteins, along with the tail subunit Sin4p, also contributes to the recruitment of mediator by Gcn4p to target promoters in vivo [3].
  • Second, mutation of pgd1 causes partial disruption of the Sin4 complex and leads to a defect in transcription reinitiation [4].
  • These results show that function of the Sin4 complex is not essential for transcription activation in a crude in vitro system but that it plays key roles in the general transcription mechanism [4].
  • We find that disruption of SIN4 allows this strain to grow at a reasonable rate, indicating a critical role for Sin4 in detecting structural changes in chromatin mediated by Gcn5 and Nhp6 [5].
 

Biological context of SIN4

  • Recessive mutations in the ARE genes cause partial loss of a-specific gene repression and cause pleiotropic phenotypes similar to those resulting from mutations in SSN6, TUP1, or SIN4, suggesting that the ARE genes are general negative regulators [6].
  • The yeast SIN4 gene functions in the transcriptional activation and repression of diverse yeast genes [7].
  • 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 by artificial reporter genes [8].
  • Mutations in SIN3 and RPD3, which encode components of a histone deacetylase complex, show the same pattern of genetic suppression, and this suppression pattern differs from that seen in a sin4 mutant [5].
  • In this study, we show that SIN4 contributes to NRE(DIT)-mediated repression, suggesting that changes in chromatin structure are, at least in part, responsible for regulation of DIT gene expression [9].
 

Associations of SIN4 with chemical compounds

 

Regulatory relationships of SIN4

 

Other interactions of SIN4

  • SSN genes that affect transcriptional repression in Saccharomyces cerevisiae encode SIN4, ROX3, and SRB proteins associated with RNA polymerase II [12].
  • SIN4, another general negative regulator, is required for this repression, but unlike tup1 or ssn6 deletions, sin4 deletions cause only partial loss of repression [6].
  • Gal11 is a general activator of basal transcription, whose activity is regulated by the general repressor Sin4 in yeast [13].
  • The sin4 delta mutant also shows phenotypes common to histone and spt mutants, including suppression of delta insertion mutations in the HIS4 and LYS2 promoters, expression of promoters lacking upstream activation sequence elements, and decreased superhelical density of circular DNA molecules [14].
  • Transcription of the CTS1 gene is reduced in sin4 delta mutants, suggesting that Sin4 functions as a positive transcriptional regulator [14].
 

Analytical, diagnostic and therapeutic context of SIN4

  • S1 mapping and Northern blot results for tsf3 suggest that the molecular defect is at the transcriptional level [15].

References

  1. Global alterations in chromatin accessibility associated with loss of SIN4 function. Macatee, T., Jiang, Y.W., Stillman, D.J., Roth, S.Y. Nucleic Acids Res. (1997) [Pubmed]
  2. Yeast global transcriptional regulators Sin4 and Rgr1 are components of mediator complex/RNA polymerase II holoenzyme. Li, Y., Bjorklund, S., Jiang, Y.W., Kim, Y.J., Lane, W.S., Stillman, D.J., Kornberg, R.D. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  3. A triad of subunits from the Gal11/tail domain of Srb mediator is an in vivo target of transcriptional activator Gcn4p. Zhang, F., Sumibcay, L., Hinnebusch, A.G., Swanson, M.J. Mol. Cell. Biol. (2004) [Pubmed]
  4. Activator-independent functions of the yeast mediator sin4 complex in preinitiation complex formation and transcription reinitiation. Reeves, W.M., Hahn, S. Mol. Cell. Biol. (2003) [Pubmed]
  5. Architectural transcription factors and the SAGA complex function in parallel pathways to activate transcription. Yu, Y., Eriksson, P., Stillman, D.J. Mol. Cell. Biol. (2000) [Pubmed]
  6. Identification of genes required for alpha 2 repression in Saccharomyces cerevisiae. Wahi, M., Johnson, A.D. Genetics (1995) [Pubmed]
  7. Regulation of HIS4 expression by the Saccharomyces cerevisiae SIN4 transcriptional regulator. Jiang, Y.W., Stillman, D.J. Genetics (1995) [Pubmed]
  8. Nuclear proteins Nut1p and Nut2p cooperate to negatively regulate a Swi4p-dependent lacZ reporter gene in Saccharomyces cerevisiae. Tabtiang, R.K., Herskowitz, I. Mol. Cell. Biol. (1998) [Pubmed]
  9. Spe3, which encodes spermidine synthase, is required for full repression through NRE(DIT) in Saccharomyces cerevisiae. Friesen, H., Tanny, J.C., Segall, J. Genetics (1998) [Pubmed]
  10. Mutations in SIN4 and RGR1 cause constitutive expression of MAL structural genes in Saccharomyces cerevisiae. Wang, X., Michels, C.A. Genetics (2004) [Pubmed]
  11. A PDR5-independent pathway of multi-drug resistance regulated by the SIN4 gene product. Fleckenstein, A., Shallom, J., Golin, J. Yeast (1999) [Pubmed]
  12. SSN genes that affect transcriptional repression in Saccharomyces cerevisiae encode SIN4, ROX3, and SRB proteins associated with RNA polymerase II. Song, W., Treich, I., Qian, N., Kuchin, S., Carlson, M. Mol. Cell. Biol. (1996) [Pubmed]
  13. Gal11 is a general activator of basal transcription, whose activity is regulated by the general repressor Sin4 in yeast. Mizuno, T., Harashima, S. Mol. Genet. Genomics (2003) [Pubmed]
  14. Involvement of the SIN4 global transcriptional regulator in the chromatin structure of Saccharomyces cerevisiae. Jiang, Y.W., Stillman, D.J. Mol. Cell. Biol. (1992) [Pubmed]
  15. TSF1 to TSF6, required for silencing the Saccharomyces cerevisiae GAL genes, are global regulatory genes. Chen, S., West, R.W., Ma, J., Johnson, S.L., Gans, H., Woldehawariat, G. Genetics (1993) [Pubmed]
 
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