In Saccharomyces cerevisiae , the heat shock transcription factor Hsf1 is kept under tight negative regulation to restrain its highly potent transcriptional activities. Recent work in our laboratory has uncovered a role for the Protein Kinase A in repressing constitutive activity of Hsf1 at two small heat shock genes, HSP26 and HSP12 by an unknown mechanism. Using a candidate gene approach, I have demonstrated that two PKA effectors, the kinase Rim15 and the transcription factor Gis1, are required for PKA-mediated repression by reducing occupancy of Hsf1 at cognate promoter elements. The cooperative function of Gis1 at these Hsf1-dependent promoters applies to constitutive and heat-inducible Hsf1 activity as, in a related project, I discovered that the kinase SCH9 is required to properly attenuate expression of the same small Hsps during heat shock. Proper attenuation requires both RIM15 and GIS1 in newly-identified roles during the heat shock response and in the presence of active PKA. These results identify the first protein regulator of heat-inducible Hsf1 activity (Sch9) and a third cooperative factor (Gis1) required for negative regulation of Hsf1 at specific heat-inducible promoters under stress and non-stress conditions.
