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| Status |
Public on Sep 05, 2023 |
| Title |
Unraveling the Mechanism of Thermotolerance in Cryptococcus neoformans by Set3C Complex |
| Organism |
Cryptococcus neoformans |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
performed paired-end RNA-seq of Cryptococcus neoformans H99s as Control group and set302∆ strains as in 100ml YPD broth at OD600=1 at 30°C or 39°C, respectively in biological triplicates.
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| Citation(s) |
38874428 |
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| Submission date |
Aug 31, 2023 |
| Last update date |
Aug 28, 2024 |
| Contact name |
XinDi Gao |
| E-mail(s) |
gaoxindi123@gmail.com
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| Phone |
18940091334
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| Organization name |
Northeastern university
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| Street address |
89, North WenHua Road
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| City |
Shenyang City, Liaoning Province |
| State/province |
Liaoning |
| ZIP/Postal code |
110004 |
| Country |
China |
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| Platforms (1) |
| GPL19081 |
Illumina HiSeq 2500 (Cryptococcus neoformans) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA1011339 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE242109_RAW.tar |
390.0 Kb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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