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.
Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720, USA.
Oliver A
OA
Zill
Jasper
J
Rine
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