Swi4-dependent SWI4 transcription couples cell size to cell cycle commitment

Growth-dependent accumulation of the limiting SBF transcription factor, composed of Swi4 and Swi6, occurs in G1 phase in budding yeast and is limiting for commitment to division, termed Start. Here we measure size-dependence of Swi4 protein copy number under different genetic contexts using a quantitative scanning number and brightness technique. Mutation of SBF binding sites in the SWI4 promoter or disruption of SBF activation resulted in ~33-50% decrease in Swi4 accumulation rate and concordantly increased cell size at Start. Ectopic inducible expression of Swi4 in G1 phase cells increased production of Swi4 from the endogenous promoter, upregulated transcription of the G1/S regulon, and accelerated Start. Despite the potential for Swi4 positive feedback, G1 phase Swi4 accumulation was linear unless the Whi5 transcriptional repressor was inactivated. A threshold model in which Swi4 titrates SBF binding sites in G1/S promoters predicted the effects of nutrients, ploidy, and G1/S regulatory mutations on cell size. These results exemplify how transcription factor auto-production can refine a cell state transition. RNA-seq analysis of estradiol-induced SWI4 overexpression in S. cerevisiae along with pre-induction and mock induced (ethanol treated) controls.