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Gene Review

SIN3  -  Sin3p

Saccharomyces cerevisiae S288c

Synonyms: CPE1, GAM2, RPD1, SDI1, SDS16, ...
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High impact information on SIN3

  • We have found that S. cerevisiae Isw2 complex represses transcription of early meiotic genes during mitotic growth in a parallel pathway to Rpd3-Sin3 histone deacetylase complex [1].
  • Here, we show that Sin3 and Rpd3 are specifically required for transcriptional repression by Ume6, a DNA-binding protein that regulates genes involved in meiosis [2].
  • We also find that inactivation of the Sin3p/Rpd3p deacetylase complex leads to a high level of acetylation at the HO locus throughout the cell cycle [3].
  • Moreover, we describe a SAP30 homolog in yeast that is functionally related to Sin3 and the histone deacetylase Rpd3 [4].
  • TIS7 interacts with the mammalian SIN3 histone deacetylase complex in epithelial cells [5].

Biological context of SIN3

  • We have cloned the SIN3 gene and determined that a haploid strain with a SIN3 gene disruption is viable [6].
  • 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 [7].
  • Combinatorial regulation of phospholipid biosynthetic gene expression by the UME6, SIN3 and RPD3 genes [8].
  • In addition, sds3 mutants have phenotypes very similar to those seen in sin3 and rpd3 mutants, suggesting that it functions in the same genetic pathway [9].
  • A LexA-Sin3 fusion protein represses transcription of promoters with LexA binding sites [10].

Anatomical context of SIN3

  • SMRT originally was identified as a corepressor of unliganded retinoic acid and thyroid receptors and forms a repressive complex with a mammalian homolog of the yeast transcriptional repressor SIN3 and the HDAC-1 histone deacetylase [11].

Associations of SIN3 with chemical compounds

  • The inferred RPD1 protein contains four regions predicted to take on helix-loop-helix-like secondary structures and three regions (acidic, glutamine rich, and proline rich) reminiscent of the activating domains of transcriptional activators [12].
  • A greater reduction in REB1 activity is observed if the sin3 mutant strain is grown in media containing galactose as a carbon source [13].
  • A sin3 mutant strain lacks detectable levels of phosphatidylethanolamine and elevated levels of phosphatidylcholine (PC) and a rpd3 mutant strain has reduced levels of PC [8].
  • Complete deletions of RPD3 and the repression adapter SIN3 permitted recombination and early meiotic gene expression when replication was inhibited with hydroxyurea (HU) [14].
  • We also show that lysine 16 of histone H4 becomes deacetylated in the proximity of a chromosomal DNA double-strand break in a Sin3p-dependent manner [15].

Physical interactions of SIN3

  • The Saccharomyces cerevisiae Sin3 transcriptional repressor is part of a large multiprotein complex that includes the Rpd3 histone deacetylase [10].
  • The in vitro levels of the REB1 DNA-binding activity are reduced in extracts prepared from strains bearing a mutation in the SIN3 gene [13].
  • Identification of the Sin3-binding site in Ume6 defines a two-step process for conversion of Ume6 from a transcriptional repressor to an activator in yeast [16].
  • Mouse homologs of SIN3 have been identified through screens for proteins interacting with the mammalian Mad1 protein, a transcriptional repressor [17].

Regulatory relationships of SIN3

  • A Ume6p-binding site was identified in the promoters of genes up-regulated in the sin3 strain [18].
  • Cyclophilin A and Ess1 interact with and regulate silencing by the Sin3-Rpd3 histone deacetylase [19].
  • Two distinct promoter elements, the upstream repression sequence (URS1) and the INO1 upstream activation sequence (UASINO) both were found to be involved in enabling SIN3 to repress INO1 expression [20].

Other interactions of SIN3

  • We show that the extent of transcriptional regulation of many, apparently unrelated, genes in Saccharomyces cerevisiae is dependent on RPD1 (and RPD3 [M. Vidal and R. F. Gaber, Mol. Cell. Biol. 11:6317-6327, 1991]) [12].
  • These results are surprising given that Ume6p, Sin3p and Rpd3p are known to form a complex that represses the expression of a diverse set of yeast genes [21].
  • Regulation of INO1 was also observed in the absence of the SIN3 gene product [22].
  • The Saccharomyces cerevisiae SIN3 gene, a negative regulator of HO, contains four paired amphipathic helix motifs [6].
  • This suggests that SIN3 and SWI1 may play opposite regulatory roles in controlling expression of many yeast genes [23].

Analytical, diagnostic and therapeutic context of SIN3

  • Immunofluorescence microscopy with anti-SIN3 antibody demonstrated that SIN3 protein was present in nuclei [6].
  • We are unable to demonstrate the direct interaction of SIN3 protein with these activators using the yeast two-hybrid system or co-immunoprecipitation [24].
  • We show here that Sin3p is present in a large multiprotein complex with an apparent molecular mass, estimated by gel filtration chromatography, of greater than 2 million Da [25].
  • Here we show that growth of a Deltatrk1Deltasin3 double mutant, under K+-limiting conditions or at low pH, is Trk2p-dependent, and by Northern blot analysis we demonstrate that deletion of SIN3 results in transcriptional derepression of TRK2 [26].


  1. The Isw2 chromatin remodeling complex represses early meiotic genes upon recruitment by Ume6p. Goldmark, J.P., Fazzio, T.G., Estep, P.W., Church, G.M., Tsukiyama, T. Cell (2000) [Pubmed]
  2. Repression by Ume6 involves recruitment of a complex containing Sin3 corepressor and Rpd3 histone deacetylase to target promoters. Kadosh, D., Struhl, K. Cell (1997) [Pubmed]
  3. Cell cycle-regulated histone acetylation required for expression of the yeast HO gene. Krebs, J.E., Kuo, M.H., Allis, C.D., Peterson, C.L. Genes Dev. (1999) [Pubmed]
  4. SAP30, a novel protein conserved between human and yeast, is a component of a histone deacetylase complex. Zhang, Y., Sun, Z.W., Iratni, R., Erdjument-Bromage, H., Tempst, P., Hampsey, M., Reinberg, D. Mol. Cell (1998) [Pubmed]
  5. TIS7 interacts with the mammalian SIN3 histone deacetylase complex in epithelial cells. Vietor, I., Vadivelu, S.K., Wick, N., Hoffman, R., Cotten, M., Seiser, C., Fialka, I., Wunderlich, W., Haase, A., Korinkova, G., Brosch, G., Huber, L.A. EMBO J. (2002) [Pubmed]
  6. The Saccharomyces cerevisiae SIN3 gene, a negative regulator of HO, contains four paired amphipathic helix motifs. Wang, H., Clark, I., Nicholson, P.R., Herskowitz, I., Stillman, D.J. Mol. Cell. Biol. (1990) [Pubmed]
  7. 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]
  8. Combinatorial regulation of phospholipid biosynthetic gene expression by the UME6, SIN3 and RPD3 genes. Elkhaimi, M., Kaadige, M.R., Kamath, D., Jackson, J.C., Biliran, H., Lopes, J.M. Nucleic Acids Res. (2000) [Pubmed]
  9. Sds3 (suppressor of defective silencing 3) is an integral component of the yeast Sin3[middle dot]Rpd3 histone deacetylase complex and is required for histone deacetylase activity. Lechner, T., Carrozza, M.J., Yu, Y., Grant, P.A., Eberharter, A., Vannier, D., Brosch, G., Stillman, D.J., Shore, D., Workman, J.L. J. Biol. Chem. (2000) [Pubmed]
  10. Roles for the Saccharomyces cerevisiae SDS3, CBK1 and HYM1 genes in transcriptional repression by SIN3. Dorland, S., Deegenaars, M.L., Stillman, D.J. Genetics (2000) [Pubmed]
  11. Corepressor SMRT binds the BTB/POZ repressing domain of the LAZ3/BCL6 oncoprotein. Dhordain, P., Albagli, O., Lin, R.J., Ansieau, S., Quief, S., Leutz, A., Kerckaert, J.P., Evans, R.M., Leprince, D. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  12. RPD1 (SIN3/UME4) is required for maximal activation and repression of diverse yeast genes. Vidal, M., Strich, R., Esposito, R.E., Gaber, R.F. Mol. Cell. Biol. (1991) [Pubmed]
  13. Identification of a Saccharomyces cerevisiae DNA-binding protein involved in transcriptional regulation. Wang, H., Nicholson, P.R., Stillman, D.J. Mol. Cell. Biol. (1990) [Pubmed]
  14. Coupling of Saccharomyces cerevisiae early meiotic gene expression to DNA replication depends upon RPD3 and SIN3. Lamb, T.M., Mitchell, A.P. Genetics (2001) [Pubmed]
  15. Saccharomyces cerevisiae Sin3p facilitates DNA double-strand break repair. Jazayeri, A., McAinsh, A.D., Jackson, S.P. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  16. Identification of the Sin3-binding site in Ume6 defines a two-step process for conversion of Ume6 from a transcriptional repressor to an activator in yeast. Washburn, B.K., Esposito, R.E. Mol. Cell. Biol. (2001) [Pubmed]
  17. SIN3-dependent transcriptional repression by interaction with the Mad1 DNA-binding protein. Kasten, M.M., Ayer, D.E., Stillman, D.J. Mol. Cell. Biol. (1996) [Pubmed]
  18. Genomewide studies of histone deacetylase function in yeast. Bernstein, B.E., Tong, J.K., Schreiber, S.L. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  19. Cyclophilin A and Ess1 interact with and regulate silencing by the Sin3-Rpd3 histone deacetylase. Arévalo-Rodríguez, M., Cardenas, M.E., Wu, X., Hanes, S.D., Heitman, J. EMBO J. (2000) [Pubmed]
  20. SIN3 works through two different promoter elements to regulate INO1 gene expression in yeast. Slekar, K.H., Henry, S.A. Nucleic Acids Res. (1995) [Pubmed]
  21. Opi1p, Ume6p and Sin3p control expression from the promoter of the INO2 regulatory gene via a novel regulatory cascade. Kaadige, M.R., Lopes, J.M. Mol. Microbiol. (2003) [Pubmed]
  22. Regulation of the yeast INO1 gene. The products of the INO2, INO4 and OPI1 regulatory genes are not required for repression in response to inositol. Graves, J.A., Henry, S.A. Genetics (2000) [Pubmed]
  23. Genetic interactions between SIN3 mutations and the Saccharomyces cerevisiae transcriptional activators encoded by MCM1, STE12, and SWI1. Wang, H., Reynolds-Hager, L., Stillman, D.J. Mol. Gen. Genet. (1994) [Pubmed]
  24. The yeast SIN3 gene product negatively regulates the activity of the human progesterone receptor and positively regulates the activities of GAL4 and the HAP1 activator. Nawaz, Z., Baniahmad, C., Burris, T.P., Stillman, D.J., O'Malley, B.W., Tsai, M.J. Mol. Gen. Genet. (1994) [Pubmed]
  25. A large protein complex containing the yeast Sin3p and Rpd3p transcriptional regulators. Kasten, M.M., Dorland, S., Stillman, D.J. Mol. Cell. Biol. (1997) [Pubmed]
  26. The yeast potassium transporter TRK2 is able to substitute for TRK1 in its biological function under low K and low pH conditions. Michel, B., Lozano, C., Rodríguez, M., Coria, R., Ramírez, J., Peña, A. Yeast (2006) [Pubmed]
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