title: The S. pombe SAGA complex controls the switch from proliferation to sexual differentiation through the opposing roles of its subunits Gcn5 and Spt8.
abstract: The SAGA complex is a conserved multifunctional coactivator known to play broad roles in eukaryotic transcription. To gain new insights into its functions, we performed biochemical and genetic analyses of SAGA in the fission yeast, Schizosaccharomyces pombe. Purification of the S. pombe SAGA complex showed that its subunit composition is identical to that of Saccharomyces cerevisiae. Analysis of S. pombe SAGA mutants revealed that SAGA has two opposing roles regulating sexual differentiation. First, in nutrient-rich conditions, the SAGA histone acetyltransferase Gcn5 represses ste11(+), which encodes the master regulator of the mating pathway. In contrast, the SAGA subunit Spt8 is required for the induction of ste11(+) upon nutrient starvation. Chromatin immunoprecipitation experiments suggest that these regulatory effects are direct, as SAGA is physically associated with the ste11(+) promoter independent of nutrient levels. Genetic tests suggest that nutrient levels do cause a switch in SAGA function, as spt8Delta suppresses gcn5Delta with respect to ste11(+) derepression in rich medium, whereas the opposite relationship, gcn5Delta suppression of spt8Delta, occurs during starvation. Thus, SAGA plays distinct roles in the control of the switch from proliferation to differentiation in S. pombe through the dynamic and opposing activities of Gcn5 and Spt8.
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Dominique
authors.initials: D
authors.lastname: Helmlinger
authors.forename: Samuel
authors.initials: S
authors.lastname: Marguerat
authors.forename: Judit
authors.initials: J
authors.lastname: Villén
authors.forename: Steven P
authors.initials: SP
authors.lastname: Gygi
authors.forename: Jürg
authors.initials: J
authors.lastname: Bähler
authors.forename: Fred
authors.initials: F
authors.lastname: Winston
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015152:Blotting, Northern; D047369:Chromatin Immunoprecipitation; D013058:Mass Spectrometry; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000099224:p300-CBP-Associated Factor
chemical_list: D000123:Acetyltransferases; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C507785:SAGA complex, S cerevisiae; C071596:ste11 protein, S pombe; C501322:Gcn5 protein, S pombe; D000099224:p300-CBP-Associated Factor