Cryptococcus neoformans var. grubii
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ABSTRACT:
PROVIDER: PRJNA277182 | ENA |
REPOSITORIES: ENA
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Project description:Thermotolerance is a crucial virulence attribute for Cryptococcus neoformans, which causes fatal fungal meningitis in humans. A protein kinase, Sch9, suppresses the thermotolerance of C. neoformans but its regulatory mechanism remains unknown. Here we elucidated the Sch9-dependent and -independent signaling networks for modulating the thermotolerance of C. neoformans through a genome-wide transcriptome analysis and reverse genetics approaches. We found that more than 1,800 genes were under transcriptional control during temperature upshift. Genes encoding for molecular chaperones and heat shock proteins were mainly upregulated, while those for translation, transcription, and sterol biosynthesis were highly suppressed. In this process Sch9 was found to regulate basal or induced expression levels of some temperature-responsive genes. Interestingly we found that Sch9 was involved in transcriptional regulation of the Ire1 kinase, which is a key sensor for the unfolded protein response pathway, and was found to be involved in ER stress response. Most notably, our data demonstrated that expression of HSF1, encoding a heat shock transcription factor 1, was downregulated during temperature upshift and Sch9 suppresses its downregulation. In spite of such expression patterns, Hsf1 was essential for growth and its overexpression indeed promoted the thermotolerance of C. neoformans, suggesting dual roles of Hsf1 in thermotolerance. This idea was supported by additional transcriptome analysis with HSF1 overexpression strain, which revealed that Hsf1 served as both activator and repressor. Hsf1 promoted genes such as Hsp104 and Hsp70 (Ssa1 and Ssa2), both of which were found to be highly upregulated during temperature upshift and required for thermotolerance, while Hsf1 repressed genes involved in oxidative stress and thermotolerance.
2015-06-01 | GSE66508 | GEO
Project description:Thermotolerance is a crucial virulence attribute for Cryptococcus neoformans, which causes fatal fungal meningitis in humans. A protein kinase, Sch9, suppresses the thermotolerance of C. neoformans but its regulatory mechanism remains unknown. Here we elucidated the Sch9-dependent and -independent signaling networks for modulating the thermotolerance of C. neoformans through a genome-wide transcriptome analysis and reverse genetics approaches. We found that more than 1,800 genes were under transcriptional control during temperature upshift. Genes encoding for molecular chaperones and heat shock proteins were mainly upregulated, while those for translation, transcription, and sterol biosynthesis were highly suppressed. In this process Sch9 was found to regulate basal or induced expression levels of some temperature-responsive genes. Interestingly we found that Sch9 was involved in transcriptional regulation of the Ire1 kinase, which is a key sensor for the unfolded protein response pathway, and was found to be involved in ER stress response. Most notably, our data demonstrated that expression of HSF1, encoding a heat shock transcription factor 1, was downregulated during temperature upshift and Sch9 suppresses its downregulation. In spite of such expression patterns, Hsf1 was essential for growth and its overexpression indeed promoted the thermotolerance of C. neoformans, suggesting dual roles of Hsf1 in thermotolerance. This idea was supported by additional transcriptome analysis with HSF1 overexpression strain, which revealed that Hsf1 served as both activator and repressor. Hsf1 promoted genes such as Hsp104 and Hsp70 (Ssa1 and Ssa2), both of which were found to be highly upregulated during temperature upshift and required for thermotolerance, while Hsf1 repressed genes involved in oxidative stress and thermotolerance.
2015-06-01 | GSE66509 | GEO
Project description:Transcriptome analysis of Sch9-depedent thermotolerance mechanism reveals a dual functional heat shock transcription factor, Hsf1, in Cryptococcus neoformans [mutants]
| PRJNA277183 | ENA
Project description:Transcriptome analysis of Sch9-depedent thermotolerance mechanism reveals a dual functional heat shock transcription factor, Hsf1, in Cryptococcus neoformans
| PRJNA277178 | ENA
Project description:Thermotolerance, a key factor essential for the virulence of pathogenic fungi including Cryptococcus neoformans, remains largely unexplored in terms of its underlying mechanism. In this study, our findings demonstrate that Set3C, a widely distributed and conserved histone deacetylase complex, is required for thermotolerance in Cryptococcus neoformans. Specifically, the deletion of the core subunit Set302, responsible for the integrity of the complex, results in a significant reduction in the growth ability under high stress and the viability at extreme temperature. Moreover, the absence of Set302 leads to a decrease in the production of capsule and melanin. Transcriptomics analysis revealed that Set302 regulates a large number of genes compared to normal condition, and their expression is responsive to heat stress. Notably, we observed that Set302 positively influences the expression of genes related to ubiquitin-proteasome system (UPS) at high temperature. Using GFP-α-synuclein overexpression model, we observed a pronounced accumulation of misfolded proteins under heat stress, consequently inhibiting the thermotolerance of Cryptococcus neoformans. Furthermore, the loss of Set302 exacerbates this inhibition of thermotolerance. Interestingly, set302∆ strain exhibits a similar phenotype under proteasome stress as it does under high temperature. We also found that set302∆ strain displayed significantly reduced pathogenicity and colonization ability compared to the wild-type strain in the murine infection model. Collectively, our findings indicate that Set302 modulates the degradation of misfolded proteins through the UPS pathway, thereby affecting the thermotolerance and pathogenicity of Cryptococcus neoformans.
2023-09-05 | GSE242109 | GEO
Project description:Exposure to heat stress triggers a well-defined acute response marked by HSF1-dependent transcriptional upregulation of heat shock proteins. Cells allowed to recover acquire thermotolerance, but this adaptation is poorly understood. By quantitative proteomics, we discovered selective upregulation of HSP70-family chaperone HSPA1 and its co-factors, HSPH1 and DNAJB1, in MCF7 breast cancer cells acquiring thermotolerance. HSPA1 was found to have dual function during heat stress response: (i) during acute stress, it promotes the recruitment of the 26S proteasome to translating ribosomes, thus poising cells for rapid protein degradation and resumption of protein synthesis upon recovery; (ii) during thermotolerance, HSPA1 together with HSPH1 maintains ubiquitylated nascent/newly synthesized proteins in a soluble state required for their efficient proteasomal clearance. Consistently, deletion of HSPH1 impedes thermotolerance and esophageal tumor growth in mice, thus providing a potential explanation for the poor prognosis of digestive tract cancers with low HSPH1, and nominating HSPH1 as a cancer drug target. We propose dual roles of HSPA1 either alone or in complex with HSPH1 and DNAJB1 in promoting quality control of nascent/newly synthesized proteins and cellular thermotolerance.
2021-05-02 | PXD025123 | Pride
Project description:We performed ChIP-seq of Hsf1 under non heat shock, 5-minute heat shock and 120 minute heat shock conditions. We used the conditional chemical genetics approach known as “anchor away” (AA) to rapidly inactivate Hsf1. We coupled Hsf1-AA to and nascent RNA seq (NAC)-seq to define the genes whose expression depends on Hsf1 during heat shock.
2018-07-26 | GSE117653 | GEO
Project description:Investigation of whole genome gene expression level changes in oocytes Hsf1-/- or Hsf2-/- compared to wild-type. The mutants analyzed in this study are further described in McMillan DR, Xiao X, Shao L, Graves K, Benjamin IJ. 1998. Targeted disruption of heat shock transcription factor 1 abolishes thermotolerance and protection against heat-inducible apoptosis. J Biol Chem. 273(13):7523-8 and in McMillan DR, Christians E, Forster M, Xiao X, Connell P, Plumier JC, Zuo X, Richardson J, Morgan S, Benjamin IJ. 2002. Heat shock transcription factor 2 is not essential for embryonic development, fertility, or adult cognitive and psychomotor function in mice. Mol Cell Biol. 22(22):8005-14. A microarray study using two technical replicates of total RNA recovered from wild-type fully-grown oocytes, Hsf1 mutant fully-grown oocytes and Hsf2 mutant fully-grown oocytes. Each microarray measures the expression level of 42,586 probe sets from Mus musculus with nine 60-mer probe pairs per gene.
2011-06-30 | E-GEOD-26240 | biostudies-arrayexpress
Project description:Investigation of whole genome gene expression level changes in oocytes Hsf1-/- or Hsf2-/- compared to wild-type. The mutants analyzed in this study are further described in McMillan DR, Xiao X, Shao L, Graves K, Benjamin IJ. 1998. Targeted disruption of heat shock transcription factor 1 abolishes thermotolerance and protection against heat-inducible apoptosis. J Biol Chem. 273(13):7523-8 and in McMillan DR, Christians E, Forster M, Xiao X, Connell P, Plumier JC, Zuo X, Richardson J, Morgan S, Benjamin IJ. 2002. Heat shock transcription factor 2 is not essential for embryonic development, fertility, or adult cognitive and psychomotor function in mice. Mol Cell Biol. 22(22):8005-14.
2011-06-30 | GSE26240 | GEO
Project description:Investigation of whole genome gene expression level changes in oocytes Hsf1-/- or Hsf2-/- compared to wild-type. The mutants analyzed in this study are further described in McMillan DR, Xiao X, Shao L, Graves K, Benjamin IJ. 1998. Targeted disruption of heat shock transcription factor 1 abolishes thermotolerance and protection against heat-inducible apoptosis. J Biol Chem. 273(13):7523-8 and in McMillan DR, Christians E, Forster M, Xiao X, Connell P, Plumier JC, Zuo X, Richardson J, Morgan S, Benjamin IJ. 2002. Heat shock transcription factor 2 is not essential for embryonic development, fertility, or adult cognitive and psychomotor function in mice. Mol Cell Biol. 22(22):8005-14.
2011-06-30 | GSE26240 | GEO