The Janus transcription factor HapX controls fungal adaptation to both iron starvation and iron excess

• Fabio Gsaller ^[4] ; Peter Hortschansky ^[5] ; Sarah R Beattie ^[6] ; Veronika Klammer ^[4] ; Katja Tuppatsch ^[7] ; Beatrix E Lechner ^[4] ; Nicole Rietzschel ^[1] ; Ernst R Werner ^[8] ; Aaron A Vogan ^[2] ; Dawoon Chung ^[6] ; Ulrich Mühlenhoff ^[1] ; Masashi Kato ^[3] ; Robert A Cramer ^[6] ; Axel A Brakhage ^[7] ; Hubertus Haas ^[4]
  1. [1] Philipp University of Marburg

     Philipp University of Marburg

     Landkreis Marburg-Biedenkopf, Alemania

     
  2. [2] McMaster University

     McMaster University

     Canadá

     
  3. [3] Meijo University

     Meijo University

     Naka-ku, Japón

     
  4. [4] 1 Division of Molecular Biology, Biocenter, Innsbruck Medical University Innsbruck, Austria
  5. [5] 2 Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI) Jena, Germany
  6. [6] 3 Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth Hanover, NH, USA
  7. [7] 2 Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI) Jena, Germany; 4 Friedrich Schiller University Jena, Germany
  8. [8] 6 Division of Biological Chemistry, Biocenter, Innsbruck Medical University Innsbruck, Austria

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 33, Nº. 19, 2014, págs. 2261-2276
• Idioma: inglés
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  • 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.