MULTIPLE SW16-DEPENDENT CIS-ACTING ELEMENTS CONTROL SWI TRANSCRIPTIONTHROUGH THE CELL-CYCLE

The Saccharomyces cerevisiae SWI4 gene encodes an essential transcript ion factor which controls gene expression at the G1/S transition of th e cell cycle. SWI4 transcription itself is cell cycle regulated, and t his periodicity is crucial for the normal cell cycle regulation of HO and at least two of the G1 cyclins. Since the regulation of SWI4 is re quired for normal cell cycle progression, we have characterized cis- a nd trans-acting regulators of SWI4 transcription. Deletion analysis of the SWI4 promoter has defined a 140-bp region which is absolutely req uired for transcription and can function as a cell cycle-regulated ups tream activating sequence (UAS). The SWI4 UAS contains three potential MluI cell cycle boxes (MCBs), which are known cell cycle-regulated pr omoter elements. Deletion of all three MCBs in the SWI4 UAS decreases the level of SWI4 mRNA 10-fold in asynchronous cultures but does not a bolish periodicity. These data suggest that MCBs are involved in SWI4 UAS activity, but at least one other periodically regulated element mu st be present. Since SWI6 is known to bind to MCBs and regulate their activity, the role of SWI6 in SWI4 expression was analyzed. Although t he MCBs cannot account for the full cell cycle regulation of SWI4, mut ations in SWI6 eliminate the normal periodicity of SWI4 transcription. This suggests that the novel cell cycle-regulated element within the SWI4 promoter is also SWI6 dependent. The constitutive transcription o f SWI4 in swi6 mutant cells occurs at an intermediate level, which ind icates that SWI6 is required for the full activation and repression of SWI4 transcription through the cell cycle. It also suggests that ther e is another pathway which can activate SWI4 transcription in the abse nce of SWI6. The second activator may also target MCB elements, since SWI4 transcription drops dramatically when they are deleted.