title: SIN3-dependent transcriptional repression by interaction with the Mad1 DNA-binding protein.
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.
authors: Division of Molecular Biology and Genetics, Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City 84132, USA.
authors: M M
authors: MM
authors: Kasten
authors: D E
authors: DE
authors: Ayer
authors: D J
authors: DJ
authors: Stillman
mesh_terms: D000818:Animals; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D017405:Herpes Simplex Virus Protein Vmw65 / Q000378:metabolism; D006655:Histone Deacetylases; D046911:Macromolecular Substances; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D012333:RNA, Messenger / Q000235:genetics; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D017405:Herpes Simplex Virus Protein Vmw65; C501382:MAD1 protein, S cerevisiae; C501384:MAD1L1 protein, human; D046911:Macromolecular Substances; C501385:Mad1l1 protein, mouse; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C071731:SIN3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D006655:Histone Deacetylases