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Exploring temporal transcription regulation structure of Aspergillus fumigatus in heat shock by state space model.

ABSTRACT: BACKGROUND: The thermotolerance of Aspergillus fumigatus plays a critical role in mammalian and avian infections. Thus, the identification of its adaptation mechanism to higher temperature is very important for an efficient anti-fungal drug development as well as fundamental understanding of its pathogenesis. We explored the temporal transcription regulation structure of this pathogenic fungus under heat shock conditions using the time series microarray data reported by Nierman et al. (Nature 2005, 438:1151-1156). RESULTS: The estimated transcription regulation structure of A. fumigatus shows that the heat shock proteins are strongly negatively associated with central metabolic pathway genes such as the tricarboxylic acid cycle (TCA cycle) and carbohydrate metabolism. It was 60 min and 120 min, respectively, after the growth temperature changes from 30 degrees C (corresponding to environments of tropical soil) to 37 degrees C and 48 degrees C (corresponding to temperatures in the human body and compost, respectively) that some of genes in TCA cycle were started to be upregulated. In these points, most of heat shock proteins showed lowest expression level after heat shocks. Among the heat shock proteins, the HSP30 (AFU6G06470), a single integral plasma membrane heat shock protein, presented most active role in transcription regulation structure in both heat shock conditions of 37 degrees C and 48 degrees C. The metabolic genes associated with multiple genes in the gene regulation network showed a tendency to have opposite expression patterns of heat shock proteins. The role of those metabolic genes was second regulator in the coherent feed-forward loop type of regulation structure having heat shock protein as its first regulator. This type of regulation structure might be very advantageous for the thermal adaptation of A. fumigatus under heat shock because a small amount of heat shock proteins can rapidly magnify their regulation effect on target genes. However, the coherent feed-forward loop type of regulation of heat shock proteins with metabolic genes became less frequent with increasing temperature. This might be the reason for dramatic increase in the expression of heat shock proteins and the number of heat shock response genes at heat shock of 48 degrees C. CONCLUSION: We systemically analysed the thermal adaption mechanism of A. fumigatus by state space model with times series microarray data in terms of transcription regulation structure. We suggest for the first time that heat shock proteins might efficiently regulate metabolic genes using the coherent feed-forward loop type of regulation structure. This type of regulation structure would also be efficient for adjustment to the other stresses requiring rapid change of metabolic mode as well as thermal adaptation.

SUBMITTER: Do JH

PROVIDER: S-EPMC2714559 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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Exploring temporal transcription regulation structure of Aspergillus fumigatus in heat shock by state space model.

Do Jin Hwan JH Yamaguchi Rui R Miyano Satoru S

BMC genomics 20090708

<h4>Background</h4>The thermotolerance of Aspergillus fumigatus plays a critical role in mammalian and avian infections. Thus, the identification of its adaptation mechanism to higher temperature is very important for an efficient anti-fungal drug development as well as fundamental understanding of its pathogenesis. We explored the temporal transcription regulation structure of this pathogenic fungus under heat shock conditions using the time series microarray data reported by Nierman et al. (Na ...[more]

PMID: 19586549

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Project description:BACKGROUND: Aspergillus fumigatus is a thermotolerant human-pathogenic mold and the most common cause of invasive aspergillosis (IA) in immunocompromised patients. Its predominance is based on several factors most of which are still unknown. The thermotolerance of A. fumigatus is one of the traits which have been assigned to pathogenicity. It allows the fungus to grow at temperatures up to and above that of a fevered human host. To elucidate the mechanisms of heat resistance, we analyzed the change of the A. fumigatus proteome during a temperature shift from 30 degrees C to 48 degrees C by 2D-fluorescence difference gel electrophoresis (DIGE). To improve 2D gel image analysis results, protein spot quantitation was optimized by missing value imputation and normalization. Differentially regulated proteins were compared to previously published transcriptome data of A. fumigatus. The study was augmented by bioinformatical analysis of transcription factor binding sites (TFBSs) in the promoter region of genes whose corresponding proteins were differentially regulated upon heat shock. RESULTS: 91 differentially regulated protein spots, representing 64 different proteins, were identified by mass spectrometry (MS). They showed a continuous up-, down- or an oscillating regulation. Many of the identified proteins were involved in protein folding (chaperones), oxidative stress response, signal transduction, transcription, translation, carbohydrate and nitrogen metabolism. A correlation between alteration of transcript levels and corresponding proteins was detected for half of the differentially regulated proteins. Interestingly, some previously undescribed putative targets for the heat shock regulator Hsf1 were identified. This provides evidence for Hsf1-dependent regulation of mannitol biosynthesis, translation, cytoskeletal dynamics and cell division in A. fumigatus. Furthermore, computational analysis of promoters revealed putative binding sites for an AP-2alpha-like transcription factor upstream of some heat shock induced genes. Until now, this factor has only been found in vertebrates. CONCLUSIONS: Our newly established DIGE data analysis workflow yields improved data quality and is widely applicable for other DIGE datasets. Our findings suggest that the heat shock response in A. fumigatus differs from already well-studied yeasts and other filamentous fungi.

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Exploring temporal transcription regulation structure of Aspergillus fumigatus in heat shock by state space model.

Publications

Exploring temporal transcription regulation structure of Aspergillus fumigatus in heat shock by state space model.

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