title: Corepressor-directed preacetylation of histone H3 in promoter chromatin primes rapid transcriptional switching of cell-type-specific genes in yeast.
abstract: Switching between alternate states of gene transcription is fundamental to a multitude of cellular regulatory pathways, including those that govern differentiation. In spite of the progress in our understanding of such transitions in gene activity, a major unanswered question is how cells regulate the timing of these switches. Here, we have examined the kinetics of a transcriptional switch that accompanies the differentiation of yeast cells of one mating type into a distinct new cell type. We found that cell-type-specific genes silenced by the alpha2 repressor in the starting state are derepressed to establish the new mating-type-specific gene expression program coincident with the loss of alpha2 from promoters. This rapid derepression does not require the preloading of RNA polymerase II or a preinitiation complex but instead depends upon the Gcn5 histone acetyltransferase. Surprisingly, Gcn5-dependent acetylation of nucleosomes in the promoters of mating-type-specific genes requires the corepressor Ssn6-Tup1 even in the repressed state. Gcn5 partially acetylates the amino-terminal tails of histone H3 in repressed promoters, thereby priming them for rapid derepression upon loss of alpha2. Thus, Ssn6-Tup1 not only efficiently represses these target promoters but also functions to initiate derepression by creating a chromatin state poised for rapid activation.
authors.affiliation: Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Box G-L2, Providence, RI 02912, USA.
authors.forename: Alec M
authors.initials: AM
authors.lastname: Desimone
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Laney
mesh_terms: D002843:Chromatin / Q000378:metabolism*; D056970:Co-Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / 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; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D000099224:p300-CBP-Associated Factor
chemical_list: D002843:Chromatin; D056970:Co-Repressor Proteins; D051548:Histone Acetyltransferases; D006657:Histones; D009687:Nuclear Proteins; D009707:Nucleosomes; D012319:RNA Polymerase II; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C065455:CYC8 protein, S cerevisiae; C112006:MOT3 protein, S cerevisiae; C093107:SPT7 protein, S cerevisiae; C066502:TUP1 protein, S cerevisiae; C501392:GCN5 protein, S cerevisiae; D000099224:p300-CBP-Associated Factor