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The Janus transcription factor HapX controls fungal adaptation to both iron starvation and iron excess.
EMBO J 2014; 33(19):2261-76EJ

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+Show Affiliations

Division of Molecular Biology, Biocenter, Innsbruck Medical University, Innsbruck, Austria.Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Germany.Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.Division of Molecular Biology, Biocenter, Innsbruck Medical University, Innsbruck, Austria.Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Germany Friedrich Schiller University, Jena, Germany.Division of Molecular Biology, Biocenter, Innsbruck Medical University, Innsbruck, Austria.Institut für Zytobiologie und Zytopathologie, Philipps-Universität Marburg, Marburg, Germany.Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria.Department of Biology, McMaster University, Hamilton, ON, Canada.Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.Institut für Zytobiologie und Zytopathologie, Philipps-Universität Marburg, Marburg, Germany.Faculty of Agriculture, Meijo University, Nagoya, Japan.Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.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.Division of Molecular Biology, Biocenter, Innsbruck Medical University, Innsbruck, Austria axel.brakhage@hki-jena.de hubertus.haas@i-med.ac.at.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25092765

Citation

Gsaller, Fabio, et al. "The Janus Transcription Factor HapX Controls Fungal Adaptation to Both Iron Starvation and Iron Excess." The EMBO Journal, vol. 33, no. 19, 2014, pp. 2261-76.
Gsaller F, Hortschansky P, Beattie SR, et al. The Janus transcription factor HapX controls fungal adaptation to both iron starvation and iron excess. EMBO J. 2014;33(19):2261-76.
Gsaller, F., Hortschansky, P., Beattie, S. R., Klammer, V., Tuppatsch, K., Lechner, B. E., ... Haas, H. (2014). The Janus transcription factor HapX controls fungal adaptation to both iron starvation and iron excess. The EMBO Journal, 33(19), pp. 2261-76. doi:10.15252/embj.201489468.
Gsaller F, et al. The Janus Transcription Factor HapX Controls Fungal Adaptation to Both Iron Starvation and Iron Excess. EMBO J. 2014 Oct 1;33(19):2261-76. PubMed PMID: 25092765.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Janus transcription factor HapX controls fungal adaptation to both iron starvation and iron excess. AU - Gsaller,Fabio, AU - Hortschansky,Peter, AU - Beattie,Sarah R, AU - Klammer,Veronika, AU - Tuppatsch,Katja, AU - Lechner,Beatrix E, AU - Rietzschel,Nicole, AU - Werner,Ernst R, AU - Vogan,Aaron A, AU - Chung,Dawoon, AU - Mühlenhoff,Ulrich, AU - Kato,Masashi, AU - Cramer,Robert A, AU - Brakhage,Axel A, AU - Haas,Hubertus, Y1 - 2014/08/04/ PY - 2014/8/6/entrez PY - 2014/8/6/pubmed PY - 2015/2/13/medline KW - fungi KW - iron regulation KW - sensing KW - siderophores KW - transcription factor complex SP - 2261 EP - 76 JF - The EMBO journal JO - EMBO J. VL - 33 IS - 19 N2 - 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. SN - 1460-2075 UR - https://www.unboundmedicine.com/medline/citation/25092765/The_Janus_transcription_factor_HapX_controls_fungal_adaptation_to_both_iron_starvation_and_iron_excess_ L2 - https://doi.org/10.15252/embj.201489468 DB - PRIME DP - Unbound Medicine ER -