HEME REGULATES SOD2 TRANSCRIPTION BY ACTIVATION AND REPRESSION IN SACCHAROMYCES-CEREVISIAE

SOD2 encodes the Saccharomyces cerevisiae manganese superoxide dismuta se (MnSOD), a mitochondrial matrix protein. Heme regulates SOD2 transc ription during both fermentative and respiratory growth by three mecha nisms. First, SOD2 transcription is activated 10-fold by growth on a n on-fermentable carbon source via the heme activator protein (Hap) 2-3- 4-5 complex. Second, SOD2 transcription is repressed 90% in the absenc e of heme. Finally, Hap1p, a heme-binding, DNA-binding transcription a ctivator, is required for full SOD2 expression during growth on glucos e. Extensive mutational analysis of the SOD2 promoter reveals three ci s elements that mediate heme-dependent regulation. Interestingly, the DNA sequences necessary for repression in the absence of heme overlap those that mediate Hap1p activation. Genetic results suggest a novel r ole for Hap1p in the regulation of repression in the absence of heme.