Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression data from T cells and NK cells with and without treatment with Hsp90 inhibitor (Geldanamycin)

ABSTRACT: Hsp90 is critical for regulation of the phenotype and functional activity of human T lymphocytes and natural killer (NK) cells. Analysis of human T cells (CD4, CD8) and NK cells treated with Hsp90 inhibitor.

ORGANISM(S): Homo sapiens

SUBMITTER: Aditya Munshi

PROVIDER: E-GEOD-42253 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:The capacity to sense and transduce temperature signals pervades all aspects of biology, and temperature exerts powerful control over the development and virulence of diverse pathogens. In the leading fungal pathogen of humans, Candida albicans, temperature has a profound impact on morphogenesis, a key virulence trait. Many cues that induce the transition from yeast to filamentous growth are contingent on a minimum temperature of 37ÂºC, while further elevatation to 39ÂºC serves as an independent inducing cue. The molecular chaperone Hsp90 is a key regulator of C. albicans temperature-dependent morphogenesis, as induction of filamentous growth requires relief from Hsp90-mediated repression of the morphogenetic program. Compromise of Hsp90 function genetically, pharmacologically, or by elevated temperature induces filamentation in a manner that depends on protein kinase A (PKA) signaling, but is independent of the terminal transcription factor, Efg1. Here, we determine that despite morphological and regulatory differences, inhibition of Hsp90 induces a transcriptional profile similar to that induced by other filamentation cues, and does so in a manner that is independent of Efg1. Further, we identify Hms1 as a transcriptional regulator required for morphogenesis induced by elevated temperature or compromise of Hsp90 function. Hms1 functions downstream of the cyclin Pcl, and the cyclin-dependent kinase Pho85, both of which are required for temperature-dependent filamentation. Upon Hsp90 inhibition, Hms1 binds to DNA elements involved in filamentous growth, including UME6 and RBT5, and regulates their expression, providing a mechanism through which Pho85, Pcl1, and Hms1 govern morphogenesis. Consistent with the importance of morphogenetic flexibility with virulence, deletion of C. albicans HMS1 attenuates virulence in a metazoan model of infection. Thus, we establish a new mechanism through which Hsp90 orchestrates C. albicans morphogenesis, and define novel regulatory circuitry governing a temperature-dependent developmental program, with broad implications for temperature sensing and virulence of microbial pathogens. Genome-wide occupancy experiments (Chip-CHIP) of FLAG-tagged Hms1p from cells grown in the presence or absence of geldanamycin (GldA). Co-precipitating genomic DNA was labelled and hybridized to whole-genome tiling arrays.

Project description:The capacity to sense and transduce temperature signals pervades all aspects of biology, and temperature exerts powerful control over the development and virulence of diverse pathogens. In the leading fungal pathogen of humans, Candida albicans, temperature has a profound impact on morphogenesis, a key virulence trait. Many cues that induce the transition from yeast to filamentous growth are contingent on a minimum temperature of 37ÂºC, while further elevatation to 39ÂºC serves as an independent inducing cue. The molecular chaperone Hsp90 is a key regulator of C. albicans temperature-dependent morphogenesis, as induction of filamentous growth requires relief from Hsp90-mediated repression of the morphogenetic program. Compromise of Hsp90 function genetically, pharmacologically, or by elevated temperature induces filamentation in a manner that depends on protein kinase A (PKA) signaling, but is independent of the terminal transcription factor, Efg1. Here, we determine that despite morphological and regulatory differences, inhibition of Hsp90 induces a transcriptional profile similar to that induced by other filamentation cues, and does so in a manner that is independent of Efg1. Further, we identify Hms1 as a transcriptional regulator required for morphogenesis induced by elevated temperature or compromise of Hsp90 function. Hms1 functions downstream of the cyclin Pcl, and the cyclin-dependent kinase Pho85, both of which are required for temperature-dependent filamentation. Upon Hsp90 inhibition, Hms1 binds to DNA elements involved in filamentous growth, including UME6 and RBT5, and regulates their expression, providing a mechanism through which Pho85, Pcl1, and Hms1 govern morphogenesis. Consistent with the importance of morphogenetic flexibility with virulence, deletion of C. albicans HMS1 attenuates virulence in a metazoan model of infection. Thus, we establish a new mechanism through which Hsp90 orchestrates C. albicans morphogenesis, and define novel regulatory circuitry governing a temperature-dependent developmental program, with broad implications for temperature sensing and virulence of microbial pathogens. Two-color experimental design testing the effect of geldanamycin on wild type of delta-efg1 cells. RNA from each replicate came from independent cultures.

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Gene expression data from T cells and NK cells with and without treatment with Hsp90 inhibitor (Geldanamycin)

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