Transcription factor FfmA interacts both physically and genetically with AtrR to properly regulate gene expression in the fungus Aspergillus fumigatus

Sanjoy Paul; Mark A. Stamnes; W. Scott Moye-Rowley

doi:10.1101/2023.06.06.543935

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Transcription factor FfmA interacts both physically and genetically with AtrR to properly regulate gene expression in the fungus Aspergillus fumigatus

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Transcription factor FfmA interacts both physically and genetically with AtrR to properly regulate gene expression in the fungus Aspergillus fumigatus

Sanjoy Paul, Mark A. Stamnes and W. Scott Moye-Rowley

bioRxiv

Cold Spring Harbor Laboratory

06/07/2023

DOI: 10.1101/2023.06.06.543935

PMCID: PMC10274792

PMID: 37333080

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https://doi.org/10.1101/2023.06.06.543935View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Transcriptional regulation of azole resistance in the filamentous fungus Aspergillus fumigatus is a key step in development of this problematic clinical phenotype. We and others have previously described a C2H2-containing transcription factor called FfmA that is required for normal levels of voriconazole susceptibility and expression of an ATP-binding cassette transporter gene called abcG1 . Null alleles of ffmA exhibit a strongly compromised growth rate even in the absence of any external stress. Here we employ an acutely repressible doxycycline-off form of ffmA to rapidly deplete FfmA protein from the cell. Using this approach, we carried out RNA-seq analyses to probe the transcriptome of A. fumigatus cells that have been deprived of normal FfmA levels. We found that 2000 genes were differentially expressed upon depletion of FfmA, consistent with the wide-ranging effect of this factor on gene regulation. Chromatin immunoprecipitation coupled with high throughput DNA sequencing analysis (ChIP-seq) identified 530 genes that were bound by FfmA using two different antibodies for immunoprecipitation. More than 300 of these genes were also bound by AtrR demonstrating the striking regulatory overlap with FfmA. However, while AtrR is clearly an upstream activation protein with clear sequence specificity, our data suggest that FfmA is a chromatin-associated factor that may bind to DNA in a manner dependent on other factors. We provide evidence that AtrR and FfmA interact in the cell and can influence one another’s expression. This interaction of AtrR and FfmA is required for normal azole resistance in A. fumigatus .

Details

Title: Subtitle: Transcription factor FfmA interacts both physically and genetically with AtrR to properly regulate gene expression in the fungus Aspergillus fumigatus
Creators: Sanjoy Paul - University of Iowa
Mark A. Stamnes - University of Iowa
W. Scott Moye-Rowley - University of Iowa
Resource Type: Preprint
Publication Details: bioRxiv
DOI: 10.1101/2023.06.06.543935
PMID: 37333080
PMCID: PMC10274792
Publisher: Cold Spring Harbor Laboratory
Language: English
Date posted: 06/07/2023
Academic Unit: Molecular Physiology and Biophysics; Internal Medicine
Record Identifier: 9984436279802771

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