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.
Pinkham JL., Wang Z., and Alsina J. Heme regulates SOD2 transcription by activation and repression in Saccharomyces cerevisiae. Current Genetics (1997) 31(4):281-91.