title: Gis1 and Rph1 regulate glycerol and acetate metabolism in glucose depleted yeast cells.
abstract: Aging in organisms as diverse as yeast, nematodes, and mammals is delayed by caloric restriction, an effect mediated by the nutrient sensing TOR, RAS/cAMP, and AKT/Sch9 pathways. The transcription factor Gis1 functions downstream of these pathways in extending the lifespan of nutrient restricted yeast cells, but the mechanisms involved are still poorly understood. We have used gene expression microarrays to study the targets of Gis1 and the related protein Rph1 in different growth phases. Our results show that Gis1 and Rph1 act both as repressors and activators, on overlapping sets of genes as well as on distinct targets. Interestingly, both the activities and the target specificities of Gis1 and Rph1 depend on the growth phase. Thus, both proteins are associated with repression during exponential growth, targeting genes with STRE or PDS motifs in their promoters. After the diauxic shift, both become involved in activation, with Gis1 acting primarily on genes with PDS motifs, and Rph1 on genes with STRE motifs. Significantly, Gis1 and Rph1 control a number of genes involved in acetate and glycerol formation, metabolites that have been implicated in aging. Furthermore, several genes involved in acetyl-CoA metabolism are downregulated by Gis1.
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Jakub
authors.initials: J
authors.lastname: Orzechowski Westholm
authors.forename: Susanna
authors.initials: S
authors.lastname: Tronnersjö
authors.forename: Niklas
authors.initials: N
authors.lastname: Nordberg
authors.forename: Ida
authors.initials: I
authors.lastname: Olsson
authors.forename: Jan
authors.initials: J
authors.lastname: Komorowski
authors.forename: Hans
authors.initials: H
authors.lastname: Ronne
mesh_terms: D000085:Acetates / Q000378:metabolism*; D000105:Acetyl Coenzyme A / Q000378:metabolism; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D005947:Glucose / Q000172:deficiency* / Q000494:pharmacology; D005990:Glycerol / Q000378:metabolism*; D056466:Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D008957:Models, Genetic; D005810:Multigene Family / Q000235:genetics; D059372:Nucleotide Motifs / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013312:Stress, Physiological / Q000187:drug effects / Q000235:genetics; D013997:Time Factors
chemical_list: D000085:Acetates; C400296:RPH1 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D000105:Acetyl Coenzyme A; C400297:GIS1 protein, S cerevisiae; D056466:Histone Demethylases; D005947:Glucose; D005990:Glycerol