Switching transcription on and off during the yeast cell cycle: Cln/Cdc28 kinases activate bound transcription factor SBF (Swi4/Swi6) at Start, whereas Clb/Cdc28 kinases displace it from the promoter in G(2)

When yeast cells reach a critical size in late G(1) they simultaneously start budding, initiate DNA synthesis, and activate transcription of a set of genes that includes G(1) cyclins CLN1, CLN2, and many DNA synthesis genes. Cell cycle-regulated expression of CLN1, CLN2 genes is attributable to the heteromeric transcription factor complex SBF. SBF is composed of Swi4 and Swi6 and binds to the promoters of CLN1 and CLN2. Different cyclin-Cdc28 complexes have different effects on late G(1)-specific transcription. Activation of transcription at the G(1)/S boundary requires Cdc28 and one of the G(1) cyclins Cln1-Cln3, whereas repression of SBF-regulated genes in G(2) requires the association of Cdc28 with G(2)-specific cyclins Clb1-Clb4. Using in vivo genomic footprinting, we show that SBF (Swi4/Swi6) binding to SCB elements (Swi4/Swi6 cell cycle box) in the CLN2 promoter is cell cycle regulated. SBF binds to the promoter prior to the activation of transcription in late G(1), suggesting that Cln/Cdc28 kinase regulates the ability of previously bound SBF to activate transcription. In contrast, SBF dissociates from the CLN2 promoter when transcription is repressed during G(2) and M phases, suggesting that Clb1-Clb4 repress SBF activity by inhibiting its DNA-binding activity. Switching transcription on and off by different mechanisms could be important to ensure that Clns are activated only once per cell cycle and could be a conserved feature of cell cycle-regulated transcription.