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

• Published in: iScience Vol. 28; no. 3; p. 112027
• Main Authors: Goswami, Pooja, Ghimire, Abhishek, Coffin, Carleton, Cheng, Jing, Coulombe-Huntington, Jasmin, Ghazal, Ghada, Thattikota, Yogitha, Guerra, María Florencia, Tyers, Mike, Tollis, Sylvain, Royer, Catherine A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.03.2025; Elsevier
• Subjects: Cell biology; Molecular biology; Cell biology; Molecular biology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2025.112027

Growth-dependent accumulation of the G1/S transcription factor SBF, composed of Swi4 and Swi6, occurs in G1 phase in budding yeast and is limiting for commitment to division, termed Start. Here, we investigate the mechanisms for the size dependence of Swi4 accumulation using different genetic contexts and quantitative scanning number and brightness microscopy. 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. 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. [Display omitted] •Swi4 protein activates SWI4 transcription in a Swi4 binding site dependent manner•Ectopic expression of Swi4 induces SWI4 expression and accelerates the G1/S transition•Quantitative microscopy suggests a copy-number threshold Swi4 is required for Start•A Swi4 threshold predicts cell size in different genetic and nutritional contexts Molecular biology; Cell biology