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Aspergillus fumigatus ZnfA, a novel zinc finger transcription factor involved in calcium metabolism and caspofungin tolerance

ABSTRACT: Aspergillus fumigatus ZnfA, a novel zinc finger transcription factor involved in calcium metabolism and caspofungin tolerance

PROVIDER: PRJNA705221 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13799049.fastq.gz	Fastqsanger.gz
	SRR13799050.fastq.gz	Fastqsanger.gz
	SRR13799051.fastq.gz	Fastqsanger.gz
	SRR13799052.fastq.gz	Fastqsanger.gz
	SRR13799053.fastq.gz	Fastqsanger.gz

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Aspergillus fumigatus ZnfA, a novel zinc finger transcription factor involved in calcium metabolism and caspofungin tolerance

Project description:Invasive Pulmonary Aspergillosis (IPA) is a life-threatening fungal infection especially in immunocompromised population. The low availability of antifungal drugs coupled with the emergence of antifungal resistance has become an important clinical concern. Caspofungin (CSP) is recommended as second-line therapy but resistance and tolerance mechanisms have been reported. However, how the fungal cell articulates the response to CSP is not completely understood. In this work we have characterized ZnfA, a new transcription factor (TF) identified in previous screening studies that is involved in calcium and CSP A. fumigatus response. This TF plays an important role in iron homeostasis and cell wall organization in response to high CSP concentrations as revealed by Chromatin Immunoprecipitation coupled to DNA sequencing (ChIP-seq) analysis. Furthermore, ZnfA acts collaboratively with the key TF CrzA in the response to calcium, cell wall and osmotic stresses. Thus, this study increases our knowledge about the link between calcium signaling and the CSP cellular response and exposes the complex connections among different pathways that govern stress sensing in A. fumigatus.

2021-10-04 | GSE167847 | GEO

Heterogeneity in the transcriptional response of the human pathogen Aspergillus fumigatus to the antifungal agent caspofungin

Project description:The transcription factor CrzA influences cell wall organization in the pathogenic fungus Aspergillus fumigatus, and also binds to the promoter regions of chitin synthase genes upon exposure to the antifungal drug caspofungin. To gain an overview of the genes directly regulated by CrzA, the CrzA binding sites were determined genome-wide by ChIP-seq

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<i>Aspergillus Fumigatus</i> ZnfA, a Novel Zinc Finger Transcription Factor Involved in Calcium Metabolism and Caspofungin Tolerance.

Project description:Invasive pulmonary aspergillosis is a life-threatening fungal infection especially in the immunocompromised patients. The low diversity of available antifungal drugs coupled with the emergence of antifungal resistance has become a worldwide clinical concern. The echinocandin Caspofungin (CSP) is recommended as a second-line therapy but resistance and tolerance mechanisms have been reported. However, how the fungal cell articulates the response to CSP is not completely understood. This work provides a detailed characterization of ZnfA, a transcription factor (TF) identified in previous screening studies that is involved in the A. fumigatus responses to calcium and CSP. This TF plays an important role in the regulation of iron homeostasis and cell wall organization in response to high CSP concentrations as revealed by Chromatin Immunoprecipitation coupled to DNA sequencing (ChIP-seq) analysis. Furthermore, ZnfA acts collaboratively with the key TF CrzA in modulating the response to calcium as well as cell wall and osmotic stresses. This study therefore describes the existence of an additional, previously unknown TF that bridges calcium signaling and the CSP cellular response and further exposes the complex connections that exist among different pathways which govern stress sensing and signaling in A. fumigatus.

| S-EPMC10512341 | biostudies-literature

Microarray of Aspergillus fumigatus wild type and ΔcrpA grown at different zinc concentrations.

Project description:Gene expression profiling of Aspergillus fumigatus comparing controls grown at normal zinc concentration of aspergillus minimum media (77uM), low (1uM) and high (500uM) zinc concentrations.

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2016-10-25 | E-GEOD-76495 | biostudies-arrayexpress

Multiparameter functional diversity of human C2H2 zinc finger proteins [RNA-Seq]

2016-10-25 | GSE76495 | GEO

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Off-Target Analysis of Zinc Finger Nucleases

Project description:Zinc Finger Nucleases (ZFNs) facilitate precise editing of DNA enabling targeted genomic modifications in vivo. ZFNs have been employed to obtain genetically modified plants and animals, and cell-based therapies utilizing ZFNs are undergoing clinical trials. However, many ZFNs display dose-dependent toxicity presumably due to the generation of undesired double stranded breaks at off-target sites within the genome. To evaluate the parameters influencing the functional specificity of ZFNs, we compared the in vivo activity of ZFN variants targeting the zebrafish kdrl locus, which display both high on-target activity and dose-dependent toxicity. We evaluated their functional specificity by assessing lesion frequency at 141 potential off-target sites within the zebrafish genome using Illumina sequencing. Only a minority of these off-target sites displayed significant lesion frequency with kdrl ZFNs. Furthermore, we find that active off-target sites appear to be defined by the thermodynamics of zinc finger-DNA recognition. Surprisingly, we observed that the zinc finger protein specificity and the choice of the engineered dimerization domain of the FokI nuclease could independently influence the fidelity of these ZFNs. The results of this study have implications for the assessment of likely off-target sites within a genome and point to both ZFP-dependent and –independent mechanisms of potential improvement for engineering ZFNs with higher levels of precision. Examined lesions at 141 off-target sites for various treatments of ZFNs and compare to the untreated sample stage 1: raw read but missing quality values stage 2: fastq files available from SRA

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Project description:A zinc finger protein (At3g62900) was identified as a putative signalling factor mediating gene regulation to reactive electrophilic oxylipin. We used microarrays to investigate the effect of a defect in the zinc finger on gene expression.

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Multiparameter functional diversity of human C2H2 zinc finger proteins

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