Heme regulates SOD2 transcription by activation and repression in Saccharomyces cerevisiae

SOD2 encodes the Saccharomyces cerevisiae manganese superoxide dismutase (MnSOD), a mitochondrial matrix protein. Heme regulates SOD2 transcription during both fermentative and respiratory growth by three mechanisms. First, SOD2 transcription is activated 10-fold by growth on a non-fermentable carbon source via the heme activator protein (Hap) 2-3-4-5 complex. Second, SOD2 transcription is repressed 90% in the absence of heme. Finally, Hap1p, a heme-binding, DNA-binding transcription activator, is required for full SOD2 expression during growth on glucose. Extensive mutational analysis of the SOD2 promoter reveals three cis 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 role for Hap1p in the regulation of repression in the absence of heme.