title: Heme regulates SOD2 transcription by activation and repression in Saccharomyces cerevisiae.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Lederle GRC Tower, University of Massachusetts, Box 34505, Amherst, MA 01003-4505, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Pinkham
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Alsina
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D023081:CCAAT-Binding Factor; D003470:Culture Media; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006418:Heme / Q000235:genetics / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins; D017384:Sequence Deletion; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D016385:TATA Box; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D023081:CCAAT-Binding Factor; D003470:Culture Media; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C058452:HAP1 protein, S cerevisiae; C061437:HAP4 protein, S cerevisiae; D007773:Lactates; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D006418:Heme; D013482:Superoxide Dismutase