Swi4-dependentSWI4transcription couples cell size to cell cycle commitment

Abstract

AbstractGrowth-dependent accumulation of the SBF transcription factor, composed of Swi4 and Swi6, occurs as cells approach the G1/S transition (Start) in budding yeast. Here we measure size-dependence of Swi4 protein copy number under different genetic contexts using the scanning number and brightness particle counting technique. Mutation of SBF binding sites in theSWI4promoter or disruption of SBF activation resulted in ∼33-50% decrease in the rate of Swi4 accumulation with cell size. Ectopic inducible expression of Swi4 in G1 phase cells increased production of Swi4 from the endogenous promoter and concomitantly upregulated transcription of the G1/S regulon. Despite the potential for Swi4 positive feedback, Swi4 accumulated linearly through G1 phase unless the Whi5 transcriptional repressor was inactivated. A threshold level of 190 Swi4 molecules titrating SBF binding sites in G1/S promoters predicted the effects of nutrients, ploidy, and G1/S regulatory mutations on cell size. These results reveal how transcription factor auto-production can contribute to a cell state transition.