REGULATION OF A YEAST HSP70 GENE BY A CAMP RESPONSIVE TRANSCRIPTIONAL CONTROL ELEMENT

HSP70 genes exhibit complex regulation in response to stress and a varriety of cellular and developmental events. The SSA3 HSP70 gene of Saccharomyces cerevisiae is activated at the transcriptional level under conditions of nutrient limitation. Analysis of deletions revealed that cis-acting DNA sequences present immediately upstream and downstream of the previously identified heat shock elements (UAS(HS)) mediate this regulation. A 35 bp region of SSA3, distinct from UAS(HS), contains sequences capable of activating a heterologous promoter following the diauxic shift and in the stationary phase of the yeast life cycle; this region has been designated an upstream activating sequence, UAS(PDS). Expression driven by UAS(PDS) is regulated by the RAS/cAMP pathway. Reduced cAMP dependent protein kinase activity results in UAS(PDS) dependent activation of the SSA3 promoter while constitutive cAMP dependent protein kinase activity prevents UAS(PDS) mediated transcription, even under growth conditions that would normally result in full activation. Although the heat shock element alone exhibits no UAS activity under conditions in which UAS(PDS) promotes transcription, UAS(HS) interacts positively with UAS(PDS) to mediate high levels of SSA3 transcription in response to nutrient limitation and lowered intracellular cAMP concentration. This interaction is independent of the precise spacing and relative orientation of the two elements.