title: The Janus transcription factor HapX controls fungal adaptation to both iron starvation and iron excess.
abstract: Balance of physiological levels of iron is essential for every organism. In Aspergillus fumigatus and other fungal pathogens, the transcription factor HapX mediates adaptation to iron limitation and consequently virulence by repressing iron consumption and activating iron uptake. Here, we demonstrate that HapX is also essential for iron resistance via activating vacuolar iron storage. We identified HapX protein domains that are essential for HapX functions during either iron starvation or high-iron conditions. The evolutionary conservation of these domains indicates their wide-spread role in iron sensing. We further demonstrate that a HapX homodimer and the CCAAT-binding complex (CBC) cooperatively bind an evolutionary conserved DNA motif in a target promoter. The latter reveals the mode of discrimination between general CBC and specific HapX/CBC target genes. Collectively, our study uncovers a novel regulatory mechanism mediating both iron resistance and adaptation to iron starvation by the same transcription factor complex with activating and repressing functions depending on ambient iron availability.
authors.affiliation: Division of Molecular Biology, Biocenter, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Fabio
authors.initials: F
authors.lastname: Gsaller
authors.affiliation: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hortschansky
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Beattie
authors.affiliation: Division of Molecular Biology, Biocenter, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Veronika
authors.initials: V
authors.lastname: Klammer
authors.affiliation: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Germany Friedrich Schiller University, Jena, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Tuppatsch
authors.affiliation: Division of Molecular Biology, Biocenter, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Beatrix E
authors.initials: BE
authors.lastname: Lechner
authors.affiliation: Institut für Zytobiologie und Zytopathologie, Philipps-Universität Marburg, Marburg, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Rietzschel
authors.affiliation: Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Ernst R
authors.initials: ER
authors.lastname: Werner
authors.affiliation: Department of Biology, McMaster University, Hamilton, ON, Canada.
authors.forename: Aaron A
authors.initials: AA
authors.lastname: Vogan
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
authors.forename: Dawoon
authors.initials: D
authors.lastname: Chung
authors.affiliation: Institut für Zytobiologie und Zytopathologie, Philipps-Universität Marburg, Marburg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mühlenhoff
authors.affiliation: Faculty of Agriculture, Meijo University, Nagoya, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Cramer
authors.affiliation: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Germany Friedrich Schiller University, Jena, Germany axel.brakhage@hki-jena.de hubertus.haas@i-med.ac.at.
authors.forename: Axel A
authors.initials: AA
authors.lastname: Brakhage
authors.affiliation: Division of Molecular Biology, Biocenter, Innsbruck Medical University, Innsbruck, Austria axel.brakhage@hki-jena.de hubertus.haas@i-med.ac.at.
authors.forename: Hubertus
authors.initials: H
authors.lastname: Haas
mesh_terms: D000222:Adaptation, Physiological; D001228:Aspergillosis / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D001232:Aspergillus fumigatus / Q000472:pathogenicity*; D015153:Blotting, Western; D047369:Chromatin Immunoprecipitation; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D006706:Homeostasis; D047468:Immunoprecipitation; D007501:Iron / Q000378:metabolism*; D013217:Starvation; D020349:Surface Plasmon Resonance; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014617:Vacuoles / Q000378:metabolism; D014774:Virulence
chemical_list: D005656:Fungal Proteins; D014157:Transcription Factors; D007501:Iron
keywords: fungi; iron regulation; sensing; siderophores; transcription factor complex
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