A temperature-responsive network links cell shape and virulence traits in a primary fungal pathogen
Ontology highlight
ABSTRACT:
ORGANISM(S): Histoplasma capsulatum
PROVIDER: GSE47832 | GEO | 2013/06/14
SECONDARY ACCESSION(S): PRJNA208214
REPOSITORIES: GEO
Similar Datasets
Project description:Survival at host temperature is a critical trait for pathogenic microbes of humans. Thermally dimorphic fungal pathogens, including Histoplasma capsulatum, are soil fungi that undergo dramatic changes in cell shape and virulence gene expression in response to host temperature. How these organisms link changes in temperature to both morphologic development and expression of virulence traits is unknown. Here we elucidate a temperature-responsive transcriptional network in H. capsulatum, which switches from a filamentous form in the environment to a pathogenic yeast form at body temperature. The circuit is driven by three highly conserved factors, Ryp1, Ryp2, and Ryp3, that are required for yeast-phase growth at 37°C. Ryp factors belong to distinct families of proteins that control developmental transitions in fungi: Ryp1 is a member of the WOPR family of transcription factors, and Ryp2 and Ryp3 are both members of the Velvet family of proteins whose molecular function is unknown. Here we provide the first evidence that these WOPR and Velvet proteins interact, and that Velvet proteins associate with DNA to drive gene expression. Using genome-wide chromatin immunoprecipitation studies, we determine that Ryp1, Ryp2, and Ryp3 associate with a large common set of genomic loci that includes known virulence genes, indicating that the Ryp factors directly control genes required for pathogenicity in addition to their role in regulating cell morphology. We further dissect the Ryp regulatory circuit by determining that a fourth transcription factor, which we name Ryp4, is required for yeast-phase growth and gene expression, associates with DNA, and displays interdependent regulation with Ryp1, Ryp2, and Ryp3. Finally, we define cis-acting motifs that recruit the Ryp factors to their interwoven network of temperature-responsive target genes. Taken together, our results reveal a positive feedback circuit that directs a broad transcriptional switch between environmental and pathogenic states in response to temperature.
| S-EPMC3720256 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-06-14 | E-GEOD-47832 | biostudies-arrayexpress
Project description:The ability to grow at host temperature is a critical trait for most pathogenic microbes of humans. Thermally dimorphic fungal pathogens, including Histoplasma capsulatum, are a class of soil fungi that undergo a dramatic change in cell shape and virulence gene expression in response to host temperature. Here we elucidate a complex temperature-responsive network in H. capsulatum, which switches from an environmental filamentous form to a pathogenic yeast form. We dissect the circuit driven by three regulators that control yeast-phase growth, and demonstrate that these factors, including two deeply conserved Velvet family proteins of unknown function, associate with DNA. We identify and characterize a fourth regulator of this pathway, and define cis-acting motifs that recruit these transcription factors to a tightly interwoven network of temperature-responsive target genes. Our results provide the first comprehensive analysis of the complex transcriptional network that links temperature to morphology and virulence in thermally dimorphic fungi. This submission gives the chromatin immunoprecipitation results. For each of the four Ryp proteins, ChIP vs. input hybridizations were performed for three replicate immunoprecipitations from the wild-type strain and two negative control replicates from the corresponding mutant strain.
2013-06-14 | E-GEOD-47341 | biostudies-arrayexpress
Project description:The ability to grow at host temperature is a critical trait for most pathogenic microbes of humans. Thermally dimorphic fungal pathogens, including Histoplasma capsulatum, are a class of soil fungi that undergo a dramatic change in cell shape and virulence gene expression in response to host temperature. Here we elucidate a complex temperature-responsive network in H. capsulatum, which switches from an environmental filamentous form to a pathogenic yeast form. We dissect the circuit driven by three regulators that control yeast-phase growth, and demonstrate that these factors, including two deeply conserved Velvet family proteins of unknown function, associate with DNA. We identify and characterize a fourth regulator of this pathway, and define cis-acting motifs that recruit these transcription factors to a tightly interwoven network of temperature-responsive target genes. Our results provide the first comprehensive analysis of the complex transcriptional network that links temperature to morphology and virulence in thermally dimorphic fungi. This submission gives the chromatin immunoprecipitation results.
2013-06-14 | GSE47341 | GEO
Project description:The ability to grow at host temperature is a critical trait for most pathogenic microbes of humans. Thermally dimorphic fungal pathogens, including Histoplasma capsulatum, are a class of soil fungi that undergo a dramatic change in cell shape and virulence gene expression in response to host temperature. Here we elucidate a complex temperature-responsive network in H. capsulatum, which switches from an environmental filamentous form to a pathogenic yeast form. We dissect the circuit driven by three regulators that control yeast-phase growth, and demonstrate that these factors, including two deeply conserved Velvet family proteins of unknown function, associate with DNA. We identify and characterize a fourth regulator of this pathway, and define cis-acting motifs that recruit these transcription factors to a tightly interwoven network of temperature-responsive target genes. Our results provide the first comprehensive analysis of the complex transcriptional network that links temperature to morphology and virulence in thermally dimorphic fungi. This submission gives the expression profiling results. cDNA from each ryp mutants and wild-type controls was labeled with Cy5 and competitively hybridized against the Cy3-labeled pooled reference sample using H. capsulatum whole-genome 70-mer oligonucleotide microarray. For the experiments with ryp T-DNA mutants, there were 4 to 6 replicates for each strain and condition, and for the experiments with ryp knockdown strains, there were 3 to 12 replicates for each strain and condition. The T-DNA and knockdown experiments are being submitted as separate series, with samples further divided based on G217B platform version.
2013-06-14 | E-GEOD-46939 | biostudies-arrayexpress
Project description:The ability to grow at host temperature is a critical trait for most pathogenic microbes of humans. Thermally dimorphic fungal pathogens, including Histoplasma capsulatum, are a class of soil fungi that undergo a dramatic change in cell shape and virulence gene expression in response to host temperature. Here we elucidate a complex temperature-responsive network in H. capsulatum, which switches from an environmental filamentous form to a pathogenic yeast form. We dissect the circuit driven by three regulators that control yeast-phase growth, and demonstrate that these factors, including two deeply conserved Velvet family proteins of unknown function, associate with DNA. We identify and characterize a fourth regulator of this pathway, and define cis-acting motifs that recruit these transcription factors to a tightly interwoven network of temperature-responsive target genes. Our results provide the first comprehensive analysis of the complex transcriptional network that links temperature to morphology and virulence in thermally dimorphic fungi. This submission gives the expression profiling results. cDNA from each ryp mutants and wild-type controls was labeled with Cy5 and competitively hybridized against the Cy3-labeled pooled reference sample using H. capsulatum whole-genome 70-mer oligonucleotide microarray. For the experiments with ryp T-DNA mutants, there were 4 to 6 replicates for each strain and condition, and for the experiments with ryp knockdown strains, there were 3 to 12 replicates for each strain and condition. The T-DNA and knockdown experiments are being submitted as separate series, with samples further divided based on G217B platform version.
2013-06-14 | E-GEOD-46938 | biostudies-arrayexpress
Project description:The ability to grow at host temperature is a critical trait for most pathogenic microbes of humans. Thermally dimorphic fungal pathogens, including Histoplasma capsulatum, are a class of soil fungi that undergo a dramatic change in cell shape and virulence gene expression in response to host temperature. Here we elucidate a complex temperature-responsive network in H. capsulatum, which switches from an environmental filamentous form to a pathogenic yeast form. We dissect the circuit driven by three regulators that control yeast-phase growth, and demonstrate that these factors, including two deeply conserved Velvet family proteins of unknown function, associate with DNA. We identify and characterize a fourth regulator of this pathway, and define cis-acting motifs that recruit these transcription factors to a tightly interwoven network of temperature-responsive target genes. Our results provide the first comprehensive analysis of the complex transcriptional network that links temperature to morphology and virulence in thermally dimorphic fungi. This submission gives the expression profiling results.
2013-06-14 | GSE46938 | GEO
Project description:The ability to grow at host temperature is a critical trait for most pathogenic microbes of humans. Thermally dimorphic fungal pathogens, including Histoplasma capsulatum, are a class of soil fungi that undergo a dramatic change in cell shape and virulence gene expression in response to host temperature. Here we elucidate a complex temperature-responsive network in H. capsulatum, which switches from an environmental filamentous form to a pathogenic yeast form. We dissect the circuit driven by three regulators that control yeast-phase growth, and demonstrate that these factors, including two deeply conserved Velvet family proteins of unknown function, associate with DNA. We identify and characterize a fourth regulator of this pathway, and define cis-acting motifs that recruit these transcription factors to a tightly interwoven network of temperature-responsive target genes. Our results provide the first comprehensive analysis of the complex transcriptional network that links temperature to morphology and virulence in thermally dimorphic fungi. This submission gives the expression profiling results.
2013-06-14 | GSE46939 | GEO
Project description:The ability to grow at host temperature is a critical trait for most pathogenic microbes of humans. Thermally dimorphic fungal pathogens, including Histoplasma capsulatum, are a class of soil fungi that undergo a dramatic change in cell shape and virulence gene expression in response to host temperature. Here we elucidate a complex temperature-responsive network in H. capsulatum, which switches from an environmental filamentous form to a pathogenic yeast form. We dissect the circuit driven by three regulators that control yeast-phase growth, and demonstrate that these factors, including two deeply conserved Velvet family proteins of unknown function, associate with DNA. We identify and characterize a fourth regulator of this pathway, and define cis-acting motifs that recruit these transcription factors to a tightly interwoven network of temperature-responsive target genes. Our results provide the first comprehensive analysis of the complex transcriptional network that links temperature to morphology and virulence in thermally dimorphic fungi. This submission gives the expression profiling results. cDNA from each ryp mutants and wild-type controls was labeled with Cy5 and competitively hybridized against the Cy3-labeled pooled reference sample using H. capsulatum whole-genome 70-mer oligonucleotide microarray. For the experiments with ryp T-DNA mutants, there were 4 to 6 replicates for each strain and condition, and for the experiments with ryp knockdown strains, there were 3 to 12 replicates for each strain and condition. The T-DNA and knockdown experiments are being submitted as separate series, with samples further divided based on G217B platform version.
2013-06-14 | E-GEOD-46936 | biostudies-arrayexpress
Project description:The ability to grow at host temperature is a critical trait for most pathogenic microbes of humans. Thermally dimorphic fungal pathogens, including Histoplasma capsulatum, are a class of soil fungi that undergo a dramatic change in cell shape and virulence gene expression in response to host temperature. Here we elucidate a complex temperature-responsive network in H. capsulatum, which switches from an environmental filamentous form to a pathogenic yeast form. We dissect the circuit driven by three regulators that control yeast-phase growth, and demonstrate that these factors, including two deeply conserved Velvet family proteins of unknown function, associate with DNA. We identify and characterize a fourth regulator of this pathway, and define cis-acting motifs that recruit these transcription factors to a tightly interwoven network of temperature-responsive target genes. Our results provide the first comprehensive analysis of the complex transcriptional network that links temperature to morphology and virulence in thermally dimorphic fungi. This submission gives the expression profiling results. cDNA from each ryp mutants and wild-type controls was labeled with Cy5 and competitively hybridized against the Cy3-labeled pooled reference sample using H. capsulatum whole-genome 70-mer oligonucleotide microarray. For the experiments with ryp T-DNA mutants, there were 4 to 6 replicates for each strain and condition, and for the experiments with ryp knockdown strains, there were 3 to 12 replicates for each strain and condition. The T-DNA and knockdown experiments are being submitted as separate series, with samples further divided based on G217B platform version.
2013-06-14 | E-GEOD-46937 | biostudies-arrayexpress