Regulation of Cell Size by Glucose Is Exerted via Repression of the CLN1 Promoter

Yeast cells are keenly sensitive to the availability and quality of nutrients. Addition of glucose to cells growing on a poorer carbon source elicits a cell cycle delay during G1 phase and a concomitant increase in the cell size. The signal is transduced through theRAS -cyclic AMP pathway. Using synchronized populations of G1 cells, we show that the increase in cell size required for budding depends uponCLN1 but not other G1 cyclins. This delay in cell cycle initiation is associated specifically with transcriptional repression ofCLN1. CLN2 is not repressed. Repression ofCLN1 is not limited to the first cycle following glucose addition but occurs in each cell cycle during growth on glucose. A 106-bp fragment of theCLN1 promoter containing the three MluI cell cycle box (MCB) core elements responsible for the majority ofCLN1 -associated upstream activation sequence activity is sufficient to confer glucose-induced repression on a heterologous reporter. A mutantCLN2 promoter that is rendered dependent upon its three MCB core elements due to inactivation of its Swi4-dependent cell cycle box (SCB) elements is also repressed by glucose. The response to glucose is partially suppressed by inactivation ofSWI4 , but notMBP1 , which is consistent with the dependence of MCB core elements upon the SCB-binding transcription factor (SBF). We suggest that differential regulation ofCLN1 andCLN2 by glucose results from differences in the capacity of SBF to activate transcription driven by SCB and MCB core elements. Finally, we show that transcriptional repression is sufficient to explain the cell cycle delay that occurs in response to glucose.