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Divergence of Transcription Factor Binding Sites in Related Yeast Species

ABSTRACT: A fundamental problem in biology is the molecular basis for divergence among related organisms. We have investigated the level of divergence of transcription factor binding sites for two key factors that regulate developmental processes in the budding yeasts. The genomic binding locations for the Ste12 and Tec1 transcription factors in S. cerevisiae, S. mikatae and S. bayanus were mapped by chromatin immunoprecipitation combined with microarrays (chIP chip)1, 2 and compared to one another. While there was a large core network which was conserved in all three species, there were many instances of binding events whose relative levels differ significantly quantitatively in one species relative to another and as well as species-specific binding events. One interesting class of genes were identified that were bound only in S. mikatae and S. bayanus; many of these genes are targets of Ste12 in haploid strains of S. cerevisiae, suggesting that S. cerevisiae has uniquely acquired the ability to differentially regulate these genes in haploid and diploid cells in these species. To extend these studies, the transcriptional network for the Ste12 homologue (Cph1) in Candida albicans was also mapped and compared to the Saccharomyces species. Again, there were several genes bound by Cph1 which are involved in mating in S. cerevisiae, suggesting that the precise delineation between many mating and pseudohyphal targets by Ste12 may be specific to S. cerevisiae. Overall our results demonstrate that transcription binding sites differ faster than gene content indicating that gene regulation at the level of transcription factor binding is likely to be a major mode of evolutionary divergence between related species. We expect that this divergence is essential for the distinct ecological niches inhabited by these organisms. Keywords: chIP-chip

ORGANISM(S): Candida albicans Saccharomyces bayanus Saccharomyces cerevisiae Saccharomyces mikatae

PROVIDER: GSE5421 | GEO | 2007/09/06

SECONDARY ACCESSION(S): PRJNA96077

REPOSITORIES: GEO

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Project description:A fundamental problem in biology is the molecular basis for divergence among related organisms. We have investigated the level of divergence of transcription factor binding sites for two key factors that regulate developmental processes in the budding yeasts. The genomic binding locations for the Ste12 and Tec1 transcription factors in S. cerevisiae, S. mikatae and S. bayanus were mapped by chromatin immunoprecipitation combined with microarrays (chIP chip)1, 2 and compared to one another. While there was a large core network which was conserved in all three species, there were many instances of binding events whose relative levels differ significantly quantitatively in one species relative to another and as well as species-specific binding events. One interesting class of genes were identified that were bound only in S. mikatae and S. bayanus; many of these genes are targets of Ste12 in haploid strains of S. cerevisiae, suggesting that S. cerevisiae has uniquely acquired the ability to differentially regulate these genes in haploid and diploid cells in these species. To extend these studies, the transcriptional network for the Ste12 homologue (Cph1) in Candida albicans was also mapped and compared to the Saccharomyces species. Again, there were several genes bound by Cph1 which are involved in mating in S. cerevisiae, suggesting that the precise delineation between many mating and pseudohyphal targets by Ste12 may be specific to S. cerevisiae. Overall our results demonstrate that transcription binding sites differ faster than gene content indicating that gene regulation at the level of transcription factor binding is likely to be a major mode of evolutionary divergence between related species. We expect that this divergence is essential for the distinct ecological niches inhabited by these organisms. Keywords: chIP-chip ChIP-chip was performed on Ste12 and Tec1 from S. cerevisiae, S. mikatae and S. bayanus in addition to Cph1 from S. cerevisiae. Three biological replicates were performed for each factor in each species with one replicate representing a dye swap.

Project description:Candida albicans can stochastically switch between two phenotypes, white and opaque. Opaque cells are the sexually competent form of C. albicans and therefore undergo efficient polarized growth and mating in the presence of pheromone. In contrast, white cells cannot mate, but are induced - under a specialized set of conditions - to form biofilms in response to pheromone. In this work, we compare the genetic regulation of such "pheromone-stimulated" biofilms with that of "conventional" C. albicans biofilms. In particular, we examined a network of six transcriptional regulators (Bcr1, Brg1, Efg1, Tec1, Ndt80, and Rob1) that mediate conventional biofilm formation for their potential roles in pheromone-stimulated biofilm formation. We show that four of the six transcription factors (Bcr1, Brg1, Rob1, and Tec1) promote formation of both conventional and pheromone-stimulated biofilms, indicating they play general roles in cell cohesion and biofilm development. In addition, we identify the master transcriptional regulator of pheromone-stimulated biofilms as C. albicans Cph1, ortholog of Saccharomyces cerevisiae Ste12. Cph1 regulates mating in C. albicans opaque cells, and here we show that Cph1 is also essential for pheromone-stimulated biofilm formation in white cells. In contrast, Cph1 is dispensable for the formation of conventional biofilms. The regulation of pheromone- stimulated biofilm formation was further investigated by transcriptional profiling and genetic analyses. These studies identified 206 genes that are induced by pheromone signaling during biofilm formation. One of these genes, HGC1, is shown to be required for both conventional and pheromone-stimulated biofilm formation. Taken together, these observations compare and contrast the regulation of conventional and pheromone-stimulated biofilm formation in C. albicans, and demonstrate that Cph1 is required for the latter, but not the former. 4 condition experiment: white and opaque cells in planktonic and pheromone-induced biofilm conditions with and without alpha pheromone. WT strain (P37005), the tec1 mutant strain and the cph1 mutant strain

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Divergence of Transcription Factor Binding Sites in Related Yeast Species

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