title: The Cyc8-Tup1 complex inhibits transcription primarily by masking the activation domain of the recruiting protein.
abstract: The yeast Tup1-Cyc8 corepressor complex is recruited to promoters by DNA-binding repressors, but the mechanisms by which it inhibits expression of genes involved in various stress pathways are poorly understood. Conditional and rapid depletion of Tup1 from the nucleus leads to concurrent nucleosome depletion and histone acetylation, recruitment of coactivators (Swi/Snf, SAGA, and Mediator), and increased transcriptional activity. Conversely, coactivator dissociation occurs rapidly upon rerepression by Cyc8-Tup1, although coactivator association and transcription can be blocked even in the absence of nucleosomes. The coactivators are recruited to the sites where Tup1 was located prior to depletion, indicating that the repressor proteins that recruit Tup1 function as activators in its absence. Last, Cyc8-Tup1 can interact with activation domains in vivo. Thus, Cyc8-Tup1 regulates transcription primarily by masking and inhibiting the transcriptional activation domains of the recruiting proteins, not by acting as a corepressor. We suggest that the corepressor function of Cyc8-Tup1 makes only a modest contribution to expression of target genes, specifically to keep expression levels below the nonactivated state.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Koon Ho
authors.initials: KH
authors.lastname: Wong
authors.forename: Kevin
authors.initials: K
authors.lastname: Struhl
mesh_terms: D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D056892:Mediator Complex / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C065455:CYC8 protein, S cerevisiae; D002868:Chromosomal Proteins, Non-Histone; C055002:GAL80 protein, S cerevisiae; D056892:Mediator Complex; D009687:Nuclear Proteins; D012097:Repressor Proteins; C507785:SAGA complex, S cerevisiae; C078562:SWI1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C066502:TUP1 protein, S cerevisiae; D015534:Trans-Activators; D014157:Transcription Factors