Project description:This SuperSeries is composed of the following subset Series: GSE32550: A conserved transcriptional regulator governs fungal morphology in widely diverged species [expression data] GSE32557: A conserved transcriptional regulator governs fungal morphology in widely diverged species [ChIP-chip, Transcriptional regulation by Mit1 and orthologs] Refer to individual Series
Project description:A conserved transcriptional regulator governs fungal morphology in widely diverged species [ChIP-chip, Transcriptional regulation by Mit1 and orthologs]
Project description:In this paper, we examine orthologs of a transcriptional regulator in three fungal species, Saccharomyces cerevisiae, Candida albicans, and Histoplasma capsulatum. We show that, despite an estimated 600 million years since those species diverged from a common ancestor, Wor1 in C. albicans, Ryp1 in H. capsulatum, and Mit1 in S. cerevisiae recognize the same DNA motif. Previous work established that Wor1 regulates white-opaque switching in C. albicans and that its ortholog Ryp1 regulates the yeast to mycelial transition in H. capsulatum. Here we show that the ortholog Mit1 in S. cerevisiae also regulates a morphological transition, in this case pseudohyphal growth. Full genome chromatin immunoprecipitation experiments show that Mit1 binds to the control regions of approximately 94 genes including the previously known regulators of pseudohyphal growth. Through a comparison of full genome chromatin immunoprecipitation experiments for Mit1 in S. cerevisiae, Wor1 in C. albicans, and Wor1 ectopically expressed in S. cerevisiae, we conclude that genes controlled by the orthologous regulators overlap only slightly between these two species. We suggest that the ancestral Wor1/Mit1/Ryp1 protein controlled aspects of cell morphology and that evolutionary movement of genes in and out of the Wor1/Mit1/Ryp1 regulon is responsible, in part, for the differences of morphological forms among these species. Consistent with this idea, ectopic expression of C. albicans Wor1 or H. capsulatum Ryp1 can drive the pseudohyphal growth program in S. cerevisiae. IP strains were compared to untagged or deletion control strains
Project description:In this paper, we examine orthologs of a transcriptional regulator in three fungal species, Saccharomyces cerevisiae, Candida albicans, and Histoplasma capsulatum. We show that, despite an estimated 600 million years since those species diverged from a common ancestor, Wor1 in C. albicans, Ryp1 in H. capsulatum, and Mit1 in S. cerevisiae recognize the same DNA motif. Previous work established that Wor1 regulates white-opaque switching in C. albicans and that its ortholog Ryp1 regulates the yeast to mycelial transition in H. capsulatum. Here we show that the ortholog Mit1 in S. cerevisiae also regulates a morphological transition, in this case pseudohyphal growth. Full genome chromatin immunoprecipitation experiments show that Mit1 binds to the control regions of approximately 94 genes including the previously known regulators of pseudohyphal growth. Through a comparison of full genome chromatin immunoprecipitation experiments for Mit1 in S. cerevisiae, Wor1 in C. albicans, and Wor1 ectopically expressed in S. cerevisiae, we conclude that genes controlled by the orthologous regulators overlap only slightly between these two species. We suggest that the ancestral Wor1/Mit1/Ryp1 protein controlled aspects of cell morphology and that evolutionary movement of genes in and out of the Wor1/Mit1/Ryp1 regulon is responsible, in part, for the differences of morphological forms among these species. Consistent with this idea, ectopic expression of C. albicans Wor1 or H. capsulatum Ryp1 can drive the pseudohyphal growth program in S. cerevisiae. Replicate experiments for each of four strains compared with reference sample - WT, a Mit1 deletion haploid A strain, a Yhr177w deletion haploid A strain, and a double deletion haploid A strain. All were in the sigma 2000 background.
Project description:Mediator is an essential, evolutionarily conserved co-regulator of RNA polymerase II. Studies in model yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe showed remarkably conserved roles for Mediator despite high species divergence, and thus whether Mediator contributed to establishment of species-specific gene expression programs within related fungal species remains an open question. Here we show that in the fungal pathogen Candida albicans, the Mediator middle domain subunit Med31 has a conserved role with non-pathogenic model yeasts in regulation of Ace2-dependent cytokinesis genes and stress responses, but also additional roles in the transcription of genes associated with virulence traits: genes related to filamentous growth and gene families expanded in pathogenic vs non-pathogenic yeasts, such as the ALS adhesins and the FGR6 family of filamentous growth regulators. Consistently, Med31 is required for two key virulence attributes of C. albicans: filamentous growth and biofilm formation. Unlike our data in C. albicans, no role for Med31 in adhesin expression has been reported in model yeasts. To show biological relevance for the control over adhesin gene expression, we demonstrate that ALS1 is a relevant Med31 target for development of biofilms. Collectively, our data supports a role for Med31 in shaping species-specific gene expression in related fungal species. Two-color experimental design comparing cells with a ?med31 mutation with a control strain in which the MED31 gene was reintroduced. RNA from each replicate came from independent cultures.
Project description:In this paper, we examine orthologs of a transcriptional regulator in three fungal species, Saccharomyces cerevisiae, Candida albicans, and Histoplasma capsulatum. We show that, despite an estimated 600 million years since those species diverged from a common ancestor, Wor1 in C. albicans, Ryp1 in H. capsulatum, and Mit1 in S. cerevisiae recognize the same DNA motif. Previous work established that Wor1 regulates white-opaque switching in C. albicans and that its ortholog Ryp1 regulates the yeast to mycelial transition in H. capsulatum. Here we show that the ortholog Mit1 in S. cerevisiae also regulates a morphological transition, in this case pseudohyphal growth. Full genome chromatin immunoprecipitation experiments show that Mit1 binds to the control regions of approximately 94 genes including the previously known regulators of pseudohyphal growth. Through a comparison of full genome chromatin immunoprecipitation experiments for Mit1 in S. cerevisiae, Wor1 in C. albicans, and Wor1 ectopically expressed in S. cerevisiae, we conclude that genes controlled by the orthologous regulators overlap only slightly between these two species. We suggest that the ancestral Wor1/Mit1/Ryp1 protein controlled aspects of cell morphology and that evolutionary movement of genes in and out of the Wor1/Mit1/Ryp1 regulon is responsible, in part, for the differences of morphological forms among these species. Consistent with this idea, ectopic expression of C. albicans Wor1 or H. capsulatum Ryp1 can drive the pseudohyphal growth program in S. cerevisiae.
Project description:In this paper, we examine orthologs of a transcriptional regulator in three fungal species, Saccharomyces cerevisiae, Candida albicans, and Histoplasma capsulatum. We show that, despite an estimated 600 million years since those species diverged from a common ancestor, Wor1 in C. albicans, Ryp1 in H. capsulatum, and Mit1 in S. cerevisiae recognize the same DNA motif. Previous work established that Wor1 regulates white-opaque switching in C. albicans and that its ortholog Ryp1 regulates the yeast to mycelial transition in H. capsulatum. Here we show that the ortholog Mit1 in S. cerevisiae also regulates a morphological transition, in this case pseudohyphal growth. Full genome chromatin immunoprecipitation experiments show that Mit1 binds to the control regions of approximately 94 genes including the previously known regulators of pseudohyphal growth. Through a comparison of full genome chromatin immunoprecipitation experiments for Mit1 in S. cerevisiae, Wor1 in C. albicans, and Wor1 ectopically expressed in S. cerevisiae, we conclude that genes controlled by the orthologous regulators overlap only slightly between these two species. We suggest that the ancestral Wor1/Mit1/Ryp1 protein controlled aspects of cell morphology and that evolutionary movement of genes in and out of the Wor1/Mit1/Ryp1 regulon is responsible, in part, for the differences of morphological forms among these species. Consistent with this idea, ectopic expression of C. albicans Wor1 or H. capsulatum Ryp1 can drive the pseudohyphal growth program in S. cerevisiae.
Project description:Fungal infections are an emerging health risk, especially those involving yeast that are resistant to antifungal agents. To understand the range of mechanisms by which yeasts can respond to anti-fungals, we compared gene expression patterns across three evolutionarily distant species - Saccharomyces cerevisiae, Candida glabrata and Kluyveromyces lactis - over time following fluconazole exposure. Conserved and diverged expression patterns were identified using a novel soft clustering algorithm that concurrently clusters data from all species while incorporating sequence orthology. The analysis suggests complementary strategies for coping with ergosterol depletion by azoles - Saccharomyces imports exogenous ergosterol, Candida exports fluconazole, while Kluyveromyces does neither leading to extreme sensitivity. In support of this hypothesis we find that only Saccharomyces becomes more azole resistant in ergosterol-supplemented media; that this depends on sterol importers Aus1 and Pdr11; and that transgenic expression of sterol importers in Kluyveromyces alleviates its drug sensitivity. We have compared the dynamic transcriptional responses of three diverse yeast species to fluconazole treatment using a novel clustering algorithm. This approach revealed significant divergence among regulatory programs associated with fluconazole sensitivity. In future, such approaches might be used to survey a wider range of species, drug concentrations and stimuli to reveal conserved and divergent molecular response pathways. There are three yeast species being studied. Each species has three biological replicates. Each biological replicate has 6 time points (0,1/3,2/3,1,2,4). These time points are combined in equal proportions to form a species and replicate specific “Reference Pool”. Each time point (except time 0) is compared against the Reference Pool. We also perform dye-swapped technical replicates for each biological replicate.
Project description:We report that a transcriptional regulator that originated in the lineage that gave rise to multiple host-associated Candida species is a key component of the circuitry that governs the C. albicans cell surface composition. Specifically, we show that the transcription regulator ZCF21 controls the expression of genes encoding multiple cell surface proteins and cell wall modifying enzymes.