Sequential Feedback Induction Stabilizes the Phosphate Starvation Response in Budding Yeast

•Cells induce the phosphate starvation response genes in two waves•The first wave acts through positive feedback to stabilize the response•The second wave acts as destabilizing negative feedback•Preventing the delay between the waves leads to transient shutdown of the response

SummaryDepletion 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.

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