title: Sequential feedback induction stabilizes the phosphate starvation response in budding yeast.
abstract: Depletion of essential nutrients triggers regulatory programs that prolong cell growth and survival. Starvation-induced processes increase nutrient transport, mobilize nutrient storage, and recycle nutrients between cellular components. This leads to an effective increase in intracellular nutrients, which may act as a negative feedback that downregulates the starvation program. To examine how cells overcome this potential instability, we followed the transcription response of budding yeast transferred to medium lacking phosphate. Genes were induced in two temporal waves. The first wave was stably maintained and persisted even upon phosphate replenishment, indicating a positive feedback loop. This commitment was abolished after 2 hr with the induction of the second expression wave, coinciding with the reduction in cell growth rate. We show that the overall temporal stability of the expression response depends on the sequential pattern of gene induction. Our results emphasize the key role of gene expression dynamics in optimizing cellular adaptation.
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Noam
authors.initials: N
authors.lastname: Vardi
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Sagi
authors.initials: S
authors.lastname: Levy
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Yonat
authors.initials: Y
authors.lastname: Gurvich
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Tamar
authors.initials: T
authors.lastname: Polacheck
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Miri
authors.initials: M
authors.lastname: Carmi
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Diego
authors.initials: D
authors.lastname: Jaitin
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Ido
authors.initials: I
authors.lastname: Amit
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: naama.barkai@weizmann.ac.il.
authors.forename: Naama
authors.initials: N
authors.lastname: Barkai
mesh_terms: D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D025461:Feedback, Physiological / Q000187:drug effects; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D005800:Genes, Fungal; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D010710:Phosphates / Q000172:deficiency* / Q000494:pharmacology; D018085:Regulon / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D004718:Saccharomycetales / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D013312:Stress, Physiological / Q000187:drug effects / Q000235:genetics; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D004268:DNA-Binding Proteins; C060292:PHO4 protein, S cerevisiae; D010710:Phosphates; D029701:Saccharomyces cerevisiae Proteins