1. The Janus transcription factor HapX controls fungal adaptation to both iron starvation and iron excess.
- Author
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Gsaller F, Hortschansky P, Beattie SR, Klammer V, Tuppatsch K, Lechner BE, Rietzschel N, Werner ER, Vogan AA, Chung D, Mühlenhoff U, Kato M, Cramer RA, Brakhage AA, and Haas H
- Subjects
- Aspergillosis genetics, Aspergillosis virology, Blotting, Western, Chromatin Immunoprecipitation, Fungal Proteins genetics, Homeostasis, Immunoprecipitation, Starvation, Surface Plasmon Resonance, Transcription Factors genetics, Vacuoles metabolism, Virulence, Adaptation, Physiological, Aspergillosis metabolism, Aspergillus fumigatus pathogenicity, Fungal Proteins metabolism, Gene Expression Regulation, Fungal, Iron metabolism, Transcription Factors metabolism
- 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., (© 2014 The Authors. Published under the terms of the CC BY 4.0 license.)
- Published
- 2014
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