Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Hypoxia response in C. neoformans in H99, CM092 and CM098

ABSTRACT: (1) The identification of genes that are transcriptionally regulated in response to exposure to hypoxia (~0.2% oxygen) in H99 (WT) and strains CM092 and CM098. (2) The identification of genes that are differentially-regulated in the strain CM093 compared to H99 (WT) Keywords: hypoxia response, comparative transcriptional hybridization 8 cultures for each strain (4 grown in normoxia and 4 grown in hypoxia) are analyzed on 4 microarrays for each strain (normoxia hybridized against hypoxia). Two out of four microarrays contain dye-swaps.

ORGANISM(S): Filobasidiella neoformans

SUBMITTER: Oliver Liu

PROVIDER: E-GEOD-6226 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

A link between virulence and homeostatic responses to hypoxia during infection by the human fungal pathogen Cryptococcus neoformans.

Chun Cheryl D CD Liu Oliver W OW Madhani Hiten D HD

PLoS pathogens 20070201 2

Fungal pathogens of humans require molecular oxygen for several essential biochemical reactions, yet virtually nothing is known about how they adapt to the relatively hypoxic environment of infected tissues. We isolated mutants defective in growth under hypoxic conditions, but normal for growth in normoxic conditions, in Cryptococcus neoformans, the most common cause of fungal meningitis. Two regulatory pathways were identified: one homologous to the mammalian sterol-response element binding pro ...[more]

PMID: 17319742

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Project description:WD40 motif-containing Msi1-like (MSIL) proteins play pleiotropic cellular functions as a negative regulator of the Ras/cAMP-pathways and a component of chromatin assembly factor-I (CAF-I), and yet have not been studied in fungal pathogens. Here we identified and characterized an MSIL protein, Msl1, in Cryptococcus neoformans, which can cause fatal meningoencephalitis in humans. Notably, Msl1 was not a functional ortholog for the yeast Msi1 but played pleiotropic roles in C. neoformans in both cAMP-dependent and -independent manners but mainly Ras-independently. Msl1 negatively controlled antioxidant melanin production and sexual differentiation, which can be repressed by inhibiting the cAMP-signaling pathways. In contrast, Msl1 controlled thermotolerance, diverse stress responses, and antifungal drugs resistance in Ras/cAMP-independent manners. Cac2, which is the second CAF-I component, appeared to play both redundant and distinct function with Msl1. Msl1 is required for full virulence of C. neoformans. Transcriptome and proteomic analysis identified a group of Msl1-regulated genes or -interacting proteins, respectively, which mostly include stress-related genes, including HSP12, HSP78, SSA1, SSA4, and STM1. Furthermore, we identified the third putative component of CAF-1, Rlf2, in C. neoformans. In conclusion, this study demonstrated the pleiotropic roles of Msl1 in human fungal pathogen C. neoformans, providing a novel antifungal therapeutic target. There is more than 95% genome homology between JEC21 and H99. Therefore, 6 slides of JEC21 (Cryptococcus neoformans var. neoformans serotype D) 70-mer oligos are used in this analysis. Total RNAs are extracted from 2 strains from H99 (H99 wild-type strain (Cryptococcus neoformans var. grubii serotype A), msl1M-NM-^T). 3 biological replicate experiments are performed for each strain. We use the mix of all total RNAs from this experiment as the control RNA. We use Cy3 as the test sample dye and Cy5 as the control dye.

Dataset Information

Hypoxia response in C. neoformans in H99, CM092 and CM098

Publications

A link between virulence and homeostatic responses to hypoxia during infection by the human fungal pathogen Cryptococcus neoformans.

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