Home LiteratureArticle Details
PMID: 8754821 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

SIN3-dependent transcriptional repression by interaction with the Mad1 DNA-binding protein.

Molecular and cellular biology ·Vol. 16 ·No. 8 ·1996-08-00 ·Pages 4215-21

Kasten MM, Ayer DE, Stillman DJ

Abstract

The SIN3 gene in Saccharomyces cerevisiae encodes a negative regulator of transcription of a large number of genes. Mouse homologs of SIN3 have been identified through screens for proteins interacting with the mammalian Mad1 protein, a transcriptional repressor. We find that yeast Sin3 (ySin3) interacts with Madl and that, as for mouse Sin3, the N terminus of Mad1 interacts with the PAH2 domain of ySin3. Although Mad1 (a basic helix-loop-helix leucine zipper [bHLH-Zip) protein) forms a heterodimer with the Max bHLH-Zip protein, LexA-Mad1 and VP16-Max do not activate transcription of a reporter gene in a two-hybrid assay. This failure in activation is due to direct repression by ySin3, as LexA-Mad1 and VP16-Max are able to activate the two-hybrid reporter in a sin3 mutant. This inhibition of activation by LexA-Mad1 and VP16-Max requires the PAH2 domain of ySin3 and the N-terminal interaction region of Mad1. These data demonstrate that ySin3 functions as a transcriptional repressor by being brought to promoters by interacting with proteins bound to DNA.

MeSH Terms
Animals Carrier Proteins Cell Cycle Proteins DNA-Binding Proteins/metabolism Fungal Proteins/metabolism Gene Expression Regulation, Fungal Herpes Simplex Virus Protein Vmw65/metabolism Histone Deacetylases Macromolecular Substances Mice Nuclear Proteins/metabolism Phosphoproteins/metabolism Protein Binding Protein Structure, Secondary RNA, Messenger/genetics Recombinant Fusion Proteins Repressor Proteins/metabolism Saccharomyces cerevisiae Proteins Transcription Factors/metabolism Transcription, Genetic
Chemicals
Carrier Proteins Cell Cycle Proteins DNA-Binding Proteins Fungal Proteins Herpes Simplex Virus Protein Vmw65 MAD1 protein, S cerevisiae MAD1L1 protein, human Macromolecular Substances Mad1l1 protein, mouse Nuclear Proteins Phosphoproteins RNA, Messenger Recombinant Fusion Proteins Repressor Proteins SIN3 protein, S cerevisiae Saccharomyces cerevisiae Proteins Transcription Factors Histone Deacetylases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Kasten M M
Division of Molecular Biology and Genetics, Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City 84132, USA.
Ayer D E
Stillman D J
References (47)
47 references, click to expand
  1. Distinct TPR motifs of Cyc8 are involved in recruiting the Cyc8-Tup1 corepressor complex to differentially regulated promoters.
    Genes Dev. 1995 Apr 1;9(7):821-31 PMID: 7705659
  2. A switch from Myc:Max to Mad:Max heterocomplexes accompanies monocyte/macrophage differentiation.
    Genes Dev. 1993 Nov;7(11):2110-9 PMID: 8224841
  3. Regulation of HIS4 expression by the Saccharomyces cerevisiae SIN4 transcriptional regulator.
    Genetics. 1995 May;140(1):103-14 PMID: 7635278
  4. Genetic and physical interactions between yeast RGR1 and SIN4 in chromatin organization and transcriptional regulation.
    Genetics. 1995 May;140(1):47-54 PMID: 7635307
  5. Contrasting roles for Myc and Mad proteins in cellular growth and differentiation.
    Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8488-92 PMID: 7667316
  6. Tetratrico peptide repeat interactions: to TPR or not to TPR?
    Trends Biochem Sci. 1995 Jul;20(7):257-9 PMID: 7667876
  7. Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor.
    Nature. 1995 Oct 5;377(6548):397-404 PMID: 7566114
  8. A transcriptional co-repressor that interacts with nuclear hormone receptors.
    Nature. 1995 Oct 5;377(6548):454-7 PMID: 7566127
  9. Specificity for the hairy/enhancer of split basic helix-loop-helix (bHLH) proteins maps outside the bHLH domain and suggests two separable modes of transcriptional repression.
    Mol Cell Biol. 1995 Dec;15(12):6923-31 PMID: 8524259
  10. Mad3 and Mad4: novel Max-interacting transcriptional repressors that suppress c-myc dependent transformation and are expressed during neural and epidermal differentiation.
    EMBO J. 1995 Nov 15;14(22):5646-59 PMID: 8521822
  11. Activation of the yeast HO gene by release from multiple negative controls.
    Cell. 1987 Feb 27;48(4):567-77 PMID: 3545494
  12. Both positive and negative regulators of HO transcription are required for mother-cell-specific mating-type switching in yeast.
    Cell. 1987 Feb 27;48(4):579-87 PMID: 3028642
  13. A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae.
    Genetics. 1989 May;122(1):19-27 PMID: 2659436
  14. DNA specificity of the bicoid activator protein is determined by homeodomain recognition helix residue 9.
    Cell. 1989 Jun 30;57(7):1275-83 PMID: 2500253
  15. Cell cycle control of the yeast HO gene: cis- and trans-acting regulators.
    Cell. 1987 Feb 13;48(3):389-97 PMID: 3542227
  16. A pleiotropic phospholipid biosynthetic regulatory mutation in Saccharomyces cerevisiae is allelic to sin3 (sdi1, ume4, rpd1).
    Genetics. 1994 Feb;136(2):475-83 PMID: 8150277
  17. Functional dissection of the yeast Cyc8-Tup1 transcriptional co-repressor complex.
    Nature. 1994 Jun 30;369(6483):758-61 PMID: 8008070
  18. The WD repeats of Tup1 interact with the homeo domain protein alpha 2.
    Genes Dev. 1994 Dec 1;8(23):2857-67 PMID: 7995523
  19. Groucho is required for Drosophila neurogenesis, segmentation, and sex determination and interacts directly with hairy-related bHLH proteins.
    Cell. 1994 Dec 2;79(5):805-15 PMID: 8001118
  20. Genetic interactions between SIN3 mutations and the Saccharomyces cerevisiae transcriptional activators encoded by MCM1, STE12, and SWI1.
    Mol Gen Genet. 1994 Dec 15;245(6):675-85 PMID: 7830715
  21. Mad-Max transcriptional repression is mediated by ternary complex formation with mammalian homologs of yeast repressor Sin3.
    Cell. 1995 Mar 10;80(5):767-76 PMID: 7889570
  22. An amino-terminal domain of Mxi1 mediates anti-Myc oncogenic activity and interacts with a homolog of the yeast transcriptional repressor SIN3.
    Cell. 1995 Mar 10;80(5):777-86 PMID: 7889571
  23. A novel genetic system to detect protein-protein interactions.
    Nature. 1989 Jul 20;340(6230):245-6 PMID: 2547163
  24. Regulated phosphorylation and dephosphorylation of GAL4, a transcriptional activator.
    Genes Dev. 1989 Aug;3(8):1157-65 PMID: 2676720
  25. Identification of negative regulatory genes that govern the expression of early meiotic genes in yeast.
    Proc Natl Acad Sci U S A. 1989 Dec;86(24):10018-22 PMID: 2690066
  26. Transcriptional regulation by dimerization: two sides to an incestuous relationship.
    Cell. 1990 Apr 6;61(1):9-11 PMID: 2180585
  27. The Saccharomyces cerevisiae SIN3 gene, a negative regulator of HO, contains four paired amphipathic helix motifs.
    Mol Cell Biol. 1990 Nov;10(11):5927-36 PMID: 2233725
  28. In vitro regulation of a SIN3-dependent DNA-binding activity by stimulatory and inhibitory factors.
    Proc Natl Acad Sci U S A. 1990 Dec;87(24):9761-5 PMID: 2263626
  29. Getting started with yeast.
    Methods Enzymol. 1991;194:3-21 PMID: 2005794
  30. Pheromone-dependent phosphorylation of the yeast STE12 protein correlates with transcriptional activation.
    Genes Dev. 1991 May;5(5):741-50 PMID: 2026326
  31. The CYC8 and TUP1 proteins involved in glucose repression in Saccharomyces cerevisiae are associated in a protein complex.
    Mol Cell Biol. 1991 Jun;11(6):3307-16 PMID: 2038333
  32. RPD1 (SIN3/UME4) is required for maximal activation and repression of diverse yeast genes.
    Mol Cell Biol. 1991 Dec;11(12):6306-16 PMID: 1944290
  33. The two-hybrid system: a method to identify and clone genes for proteins that interact with a protein of interest.
    Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9578-82 PMID: 1946372
  34. Myc and Max associate in vivo.
    Genes Dev. 1992 Jan;6(1):71-80 PMID: 1730411
  35. Ssn6-Tup1 is a general repressor of transcription in yeast.
    Cell. 1992 Feb 21;68(4):709-19 PMID: 1739976
  36. The Saccharomyces cerevisiae GAM2/SIN3 protein plays a role in both activation and repression of transcription.
    Mol Gen Genet. 1992 May;233(1-2):327-30 PMID: 1603074
  37. Myc family oncoproteins function through a common pathway to transform normal cells in culture: cross-interference by Max and trans-acting dominant mutants.
    Genes Dev. 1992 Aug;6(8):1480-92 PMID: 1644290
  38. Transcriptional activation by the human c-Myc oncoprotein in yeast requires interaction with Max.
    Nature. 1992 Oct 1;359(6394):423-6 PMID: 1406955
  39. Myc and Max proteins possess distinct transcriptional activities.
    Nature. 1992 Oct 1;359(6394):426-9 PMID: 1406956
  40. Mad: a heterodimeric partner for Max that antagonizes Myc transcriptional activity.
    Cell. 1993 Jan 29;72(2):211-22 PMID: 8425218
  41. Mxi1, a protein that specifically interacts with Max to bind Myc-Max recognition sites.
    Cell. 1993 Jan 29;72(2):223-32 PMID: 8425219
  42. Oncogenic activity of the c-Myc protein requires dimerization with Max.
    Cell. 1993 Jan 29;72(2):233-45 PMID: 8425220
  43. Transcriptional repression in Saccharomyces cerevisiae by a SIN3-LexA fusion protein.
    Mol Cell Biol. 1993 Mar;13(3):1805-14 PMID: 8441414
  44. Bipartite structure of an early meiotic upstream activation sequence from Saccharomyces cerevisiae.
    Mol Cell Biol. 1993 Apr;13(4):2172-81 PMID: 8455605
  45. Mammalian Ras interacts directly with the serine/threonine kinase Raf.
    Cell. 1993 Jul 16;74(1):205-14 PMID: 8334704
  46. BUD2 encodes a GTPase-activating protein for Bud1/Rsr1 necessary for proper bud-site selection in yeast.
    Nature. 1993 Sep 16;365(6443):269-74 PMID: 8371782
  47. Repression by SSN6-TUP1 is directed by MIG1, a repressor/activator protein.
    Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3132-6 PMID: 7724528
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.16.8.4215
Published
1996-08-00
Pages
4215-21
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC231419
Subset
IM
Grants
NCI NIH HHS · CA57138 · United States
NIGMS NIH HHS · GM39067 · United States
External Links
PubMed source DOI: 10.1128/MCB.16.8.4215 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2