Genome-wide location of Candida albicans transcription factor Rme1p
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PROVIDER: PRJNA596196 | ENA |
REPOSITORIES: ENA
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Project description:Rme1, a conserved transcription factor among members of the ascomycete lineage, regulates meiosis and pseudohyphal growth in baker’s yeast. The genome of the meiosis-defective fungal pathogen Candida albicans encodes a Rme1 homolog, which we previously mapped within a transcriptional circuitry that controls hyphal growth. To delineate a possible role of Rme1 in C. albicans morphogenesis, we combined genome-wide expression and location analyses of Rme1. Strikingly, Rme1 bound upstream and activated the expression of markers of chlamydosporulation, a process leading to formation of large, spherical, thick-walled cells during nutrient starvation. RME1 deletion abolished chlamydosporulation in three chlamydospore-forming Candida species, whereas its overexpression bypassed the requirement for chlamydosporulation cues and regulators, indicating that Rme1 is central to chlamydospore development. Moreover, RME1 expression levels correlated with chlamydosporulation efficiency among clinical isolates, further highlighting Rme1 importance in this process. Interestingly, RME1 displayed a biphasic pattern of expression, with a first phase independent of Rme1 function and dependent on chlamydospore-inducing cues, and a second phase depending upon Rme1 function and independent of chlamydospore-inducing cues. We suggest that Rme1 function spans from the regulation of meiosis in sexual yeasts to the control of an epigenetic switch necessary for asexual spore formation in meiosis-defective Candida species.
2020-10-07 | GSE142159 | GEO
Project description:Skn7 is a conserved fungal heat shock factor-type transcriptional regulator. It participates in maintaining cell wall integrity and regulates the osmotic/oxidative stress response (OSR) in S. cerevisiae, where it is part of a two-component signal transduction system. Here, we comprehensively address the function of Skn7 in the human fungal pathogen Candida albicans. We provide evidence reinforcing functional divergence, with loss of the cell wall/osmotic stress-protective roles and acquisition of the ability to regulate morphogenesis on solid medium. Mapping of the Skn7 transcriptional circuitry, through combination of genome-wide expression and location technologies, pointed to a dual regulatory role encompassing OSR and filamentous growth. Genetic interaction analyses revealed close functional interactions between Skn7 and master regulators of morphogenesis, including Efg1, Cph1 and Ume6. Intracellular biochemical assays revealed that Skn7 is crucial for limiting the accumulation of reactive oxygen species (ROS) during filamentous growth on solid medium. Interestingly, functional domain mapping using site-directed mutagenesis allowed decoupling of Skn7 function in morphogenesis from protection against intracellular ROS. Our work identifies Skn7 as an integral part of the transcriptional circuitry controlling C. albicans filamentous growth and illuminates how C. albicans relies on an evolutionarily-conserved regulator to protect itself from intracellular ROS during morphological development.
2017-06-30 | GSE85276 | GEO
Project description:Candida albicans is part of the human gastrointestinal (GI) microbiota. To better understand how C. albicans efficiently establishes GI colonisation, we competitively challenged growth of 572 signature-tagged strains (~10% genome coverage), each conditionally overexpressing a single gene, in the murine gut. We identified CRZ2, a transcription factor whose overexpression and deletion respectively increased and decreased early GI colonisation. Using clues from genome-wide expression and gene-set enrichment analyses, we found that the optimal activity of Crz2p occurs under hypoxia at 37°C, as evidenced by both phenotypic and transcriptomic analyses following CRZ2 genetic perturbation. Consistent with early colonisation of the GI tract, we show that CRZ2 overexpression confers resistance to acidic pH and bile salts, suggesting an adaptation to the upper sections of the gut. Genome-wide location analyses revealed that Crz2p directly modulates the expression of many mannosyltransferase- and cell-wall protein-encoding genes, suggesting a link with cell-wall function. We show that CRZ2 overexpression alters cell-wall phosphomannan abundance and increases sensitivity to tunicamycin, suggesting a role in protein glycosylation. Our study reflects the powerful use of gene overexpression as a complementary approach to gene deletion to identify relevant biological pathways involved in C. albicans interaction with the host environment.
2018-11-20 | GSE67233 | GEO
Project description:Rme1, a conserved transcription factor among members of the ascomycete lineage, regulates meiosis and pseudohyphal growth in baker’s yeast. The genome of the meiosis-defective fungal pathogen Candida albicans encodes a Rme1 homolog, which we previously mapped within a transcriptional circuitry that controls hyphal growth. To delineate a possible role of Rme1 in C. albicans morphogenesis, we combined genome-wide expression and location analyses of Rme1. Strikingly, Rme1 bound upstream and activated the expression of markers of chlamydosporulation, a process leading to formation of large, spherical, thick-walled cells during nutrient starvation. RME1 deletion abolished chlamydosporulation in three chlamydospore-forming Candida species, whereas its overexpression bypassed the requirement for chlamydosporulation cues and regulators, indicating that Rme1 is central to chlamydospore development. Moreover, RME1 expression levels correlated with chlamydosporulation efficiency among clinical isolates, further highlighting Rme1 importance in this process. Interestingly, RME1 displayed a biphasic pattern of expression, with a first phase independent of Rme1 function and dependent on chlamydospore-inducing cues, and a second phase depending upon Rme1 function and independent of chlamydospore-inducing cues. We suggest that Rme1 function spans from the regulation of meiosis in sexual yeasts to the control of an epigenetic switch necessary for asexual spore formation in meiosis-defective Candida species.
2020-10-07 | GSE142370 | GEO
Project description:Genome-wide location of Candida albicans transcription factor Skn7p
| PRJNA338059 | ENA
Project description:Genome-wide location of Candida albicans transcription factor Crz2p
| PRJNA279300 | ENA
Project description:Candida albicans is part of the human gastrointestinal (GI) microbiota. To better understand how C. albicans efficiently establishes GI colonisation, we competitively challenged growth of 572 signature-tagged strains (~10% genome coverage), each conditionally overexpressing a single gene, in the murine gut. We identified CRZ2, a transcription factor whose overexpression and deletion respectively increased and decreased early GI colonisation. Using clues from genome-wide expression and gene-set enrichment analyses, we found that the optimal activity of Crz2p occurs under hypoxia at 37°C, as evidenced by both phenotypic and transcriptomic analyses following CRZ2 genetic perturbation. Consistent with early colonisation of the GI tract, we show that CRZ2 overexpression confers resistance to acidic pH and bile salts, suggesting an adaptation to the upper sections of the gut. Genome-wide location analyses revealed that Crz2p directly modulates the expression of many mannosyltransferase- and cell-wall protein-encoding genes, suggesting a link with cell-wall function. We show that CRZ2 overexpression alters cell-wall phosphomannan abundance and increases sensitivity to tunicamycin, suggesting a role in protein glycosylation. Our study reflects the powerful use of gene overexpression as a complementary approach to gene deletion to identify relevant biological pathways involved in C. albicans interaction with the host environment.
2018-11-20 | GSE67226 | GEO
Project description:Skn7 is a conserved fungal heat shock factor-type transcriptional regulator. It participates in maintaining cell wall integrity and regulates the osmotic/oxidative stress response (OSR) in S. cerevisiae, where it is part of a two-component signal transduction system. Here, we comprehensively address the function of Skn7 in the human fungal pathogen Candida albicans. We provide evidence reinforcing functional divergence, with loss of the cell wall/osmotic stress-protective roles and acquisition of the ability to regulate morphogenesis on solid medium. Mapping of the Skn7 transcriptional circuitry, through combination of genome-wide expression and location technologies, pointed to a dual regulatory role encompassing OSR and filamentous growth. Genetic interaction analyses revealed close functional interactions between Skn7 and master regulators of morphogenesis, including Efg1, Cph1 and Ume6. Intracellular biochemical assays revealed that Skn7 is crucial for limiting the accumulation of reactive oxygen species (ROS) during filamentous growth on solid medium. Interestingly, functional domain mapping using site-directed mutagenesis allowed decoupling of Skn7 function in morphogenesis from protection against intracellular ROS. Our work identifies Skn7 as an integral part of the transcriptional circuitry controlling C. albicans filamentous growth and illuminates how C. albicans relies on an evolutionarily-conserved regulator to protect itself from intracellular ROS during morphological development.
2017-06-30 | GSE85275 | GEO
Project description:Background : Candida albicans is a diploid pathogenic fungus not yet amenable to routine genetic investigations. Understanding aspects of the regulation of its biological functions and the assembly of its protein complexes would lead to further insight into the biology of this common disease-causing microbial agent. Results: We have developed a toolbox allowing in vivo protein tagging by PCR-mediated homologous recombination with TAP, HA and MYC tags. The transformation cassettes were designed to accommodate a common set of integration primers. The tagged proteins can be used to perform tandem affinity purification (TAP) or chromatin immunoprecipitation coupled with microarray analysis (ChIP-CHIP). Tandem affinity purification of C. albicans Nop1 revealed the high conservation of the small processome composition in yeasts. Data obtained with in vivo TAP-tagged Tbf1, Cbf1 and Mcm1 recapitulates previously published genome-wide location profiling by ChIP-CHIP. We also designed a new reporter system for in vivo analysis of transcriptional activity of gene loci in C. albicans. Conclusion: This toolbox provides a basic setup to perform purification of protein complexes and increase the number of annotated transcriptional regulators and genetic circuits in C. albicans.
2008-11-15 | GSE13427 | GEO
Project description:Genome-wide expression profiling of Candida albicans transcription factor Rme1p
| PRJNA596766 | ENA