title: Opi1 mediates repression of phospholipid biosynthesis by phosphate limitation in the yeast Saccharomyces cerevisiae.
abstract: Structural genes of phospholipid biosynthesis in the yeast Saccharomyces cerevisiae are transcribed when precursor molecules inositol and choline (IC) are limiting. Gene expression is stimulated by the heterodimeric activator Ino2/Ino4, which binds to ICRE (inositol/choline-responsive element) promoter sequences. Activation is prevented by repressor Opi1, counteracting Ino2 when high concentrations of IC are available. Here we show that ICRE-dependent gene activation is repressed not only by an excess of IC but also under conditions of phosphate starvation. While PHO5 is activated by phosphate limitation, INO1 expression is repressed about 10-fold. Repression of ICRE-dependent genes by low phosphate is no longer observed in an opi1 mutant while repression is still effective in mutants of the PHO regulon (pho4, pho80, pho81 and pho85). In contrast, gene expression with high phosphate is reduced in the absence of pleiotropic sensor protein kinase Pho85. We could demonstrate that Pho85 binds to Opi1 in vitro and in vivo and that this interaction is increased in the presence of high concentrations of phosphate. Interestingly, Pho85 binds to two separate domains of Opi1 which have been previously shown to recruit pleiotropic corepressor Sin3 and activator Ino2, respectively. We postulate that Pho85 positively influences ICRE-dependent gene expression by phosphorylation-dependent weakening of Opi1 repressor, affecting its functional domains required for promoter recruitment and corepressor interaction. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Institut für Genetik und Funktionelle Genomforschung, Ernst-Moritz-Arndt Universität Greifswald, Jahnstr. 15a, D-17487, Greifswald, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Kliewe
authors.affiliation: Institut für Genetik und Funktionelle Genomforschung, Ernst-Moritz-Arndt Universität Greifswald, Jahnstr. 15a, D-17487, Greifswald, Germany.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Kumme
authors.affiliation: Institut für Genetik und Funktionelle Genomforschung, Ernst-Moritz-Arndt Universität Greifswald, Jahnstr. 15a, D-17487, Greifswald, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Grigat
authors.affiliation: Institut für Genetik und Funktionelle Genomforschung, Ernst-Moritz-Arndt Universität Greifswald, Jahnstr. 15a, D-17487, Greifswald, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hintze
authors.affiliation: Institut für Genetik und Funktionelle Genomforschung, Ernst-Moritz-Arndt Universität Greifswald, Jahnstr. 15a, D-17487, Greifswald, Germany.
authors.forename: Hans-Joachim
authors.identifier: 0000-0003-4080-4014
authors.initials: HJ
authors.lastname: Schüller
mesh_terms: D015966:Gene Expression Regulation, Fungal / Q000502:physiology*; D009154:Mutation; D010710:Phosphates / Q000378:metabolism*; D010743:Phospholipids / Q000096:biosynthesis*; D011485:Protein Binding; D000072417:Protein Domains; D018085:Regulon; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C096105:OPI1 protein, S cerevisiae; D010710:Phosphates; D010743:Phospholipids; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins
keywords: Opi1; Pho80; Pho85; Saccharomyces cerevisiae; phosphate starvation; phospholipid biosynthesis