Interspecies variation reveals a conserved repressor of alpha-specific genes in Saccharomyces yeasts.
The mating-type determination circuit in Saccharomyces yeast serves as a classic paradigm for the genetic control of cell type in all eukaryotes. Using comparative genetics, we discovered a central and conserved, yet previously undetected, component of this genetic circuit: active repression of alpha-specific genes in a cells. Upon inactivation of the SUM1 gene in Saccharomyces bayanus, a close relative of Saccharomyces cerevisiae, a cells acquired mating characteristics of alpha cells and displayed autocrine activation of their mating response pathway. Sum1 protein bound to the promoters of alpha-specific genes, repressing their transcription. In contrast to the standard model, alpha1 was important but not required for alpha-specific gene activation and mating of alpha cells in the absence of Sum1. Neither Sum1 protein expression, nor its association with target promoters was mating-type-regulated. Thus, the alpha1/Mcm1 coactivators did not overcome repression by occluding Sum1 binding to DNA. Surprisingly, the mating-type regulatory function of Sum1 was conserved in S. cerevisiae. We suggest that a comprehensive understanding of some genetic pathways may be best attained through the expanded phenotypic space provided by study of those pathways in multiple related organisms.
Zill
Oliver A
OA
Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720, USA.
Rine
Jasper
J
D001483:Base Sequence; D017124:Conserved Sequence; D015966:Gene Expression Regulation, Fungal; D049770:Genes, Mating Type, Fungal; D049810:Genetic Speciation; D018398:Homeodomain Proteins / Q000502:physiology; D026341:Minichromosome Maintenance 1 Protein / Q000502:physiology; D008954:Models, Biological; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000502:physiology; D030781:Organisms, Genetically Modified; D010641:Phenotype; D010802:Phylogeny; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics* / Q000502:physiology; D012440:Saccharomyces / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D014157:Transcription Factors / Q000502:physiology; D015533:Transcriptional Activation
D018398:Homeodomain Proteins; C096063:MATA1 protein, S cerevisiae; D026341:Minichromosome Maintenance 1 Protein; D009687:Nuclear Proteins; D012097:Repressor Proteins; C489241:STE12 protein, S cerevisiae; C100925:SUM1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors