title: Growth-regulated recruitment of the essential yeast ribosomal protein gene activator Ifh1.
abstract: Regulation of ribosome biogenesis is central to the control of cell growth. In rapidly growing yeast cells, ribosomal protein (RP) genes account for approximately one-half of all polymerase II transcription-initiation events, yet these genes are markedly and coordinately downregulated in response to a number of environmental stress conditions, or during the transition from fermentation to respiration. Although several conserved signalling pathways (TOR, RAS/protein kinase A and protein kinase C) impinge upon RP gene transcription, little is known about how initiation at these genes is controlled. Rap1 (refs 6, 7) and more recently Fhl1 (ref. 8) were shown to bind upstream of many RP genes. Here we show that the essential protein Ifh1 binds to and activates many RP gene promoters under optimal growth conditions in Saccharomyces cerevisiae. Ifh1 is recruited to RP gene promoters through the forkhead-associated domain of Fhl1. Ifh1 binding decreases when RP genes are downregulated either by TOR inhibition or nutrient depletion, and is restored after release from starvation or upon regulated induction of IFH1 expression. These findings indicate a central role for Ifh1 and Fhl1 in RP gene regulation.
authors.affiliation: Department of Molecular Biology and NCCR Program Frontiers in Genetics University of Geneva, Sciences III, 30, quai Ernest-Ansermet, Geneva 4, CH-1211, Switzerland.
authors.forename: Stephan B
authors.initials: SB
authors.lastname: Schawalder
authors.forename: Mehdi
authors.initials: M
authors.lastname: Kabani
authors.forename: Isabelle
authors.initials: I
authors.lastname: Howald
authors.forename: Urmila
authors.initials: U
authors.lastname: Choudhury
authors.forename: Michel
authors.initials: M
authors.lastname: Werner
authors.forename: David
authors.initials: D
authors.lastname: Shore
mesh_terms: D051858:Forkhead Transcription Factors; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D020043:Genes, Essential / Q000502:physiology*; D005800:Genes, Fungal / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D012269:Ribosomal Proteins / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism*; D000089804:Shelterin Complex; D020123:Sirolimus / Q000494:pharmacology; D034501:Telomere-Binding Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: C495776:FHL1 protein, S cerevisiae; D051858:Forkhead Transcription Factors; C094046:IFH1 protein, S cerevisiae; C440829:RAP1 protein, S cerevisiae; D012333:RNA, Messenger; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D020123:Sirolimus