Journal article
The Janus transcription factor HapX controls fungal adaptation to both iron starvation and iron excess
The EMBO journal, Vol.33(19), pp.2261-2276
10/01/2014
DOI: 10.15252/embj.201489468
PMCID: PMC4232046
PMID: 25092765
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.
Details
- Title: Subtitle
- The Janus transcription factor HapX controls fungal adaptation to both iron starvation and iron excess
- Creators
- Fabio Gsaller - Innsbruck Medical UniversityPeter Hortschansky - Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI)Sarah R. Beattie - Dartmouth CollegeVeronika Klammer - Innsbruck Medical UniversityKatja Tuppatsch - Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI)Beatrix E. Lechner - Innsbruck Medical UniversityNicole Rietzschel - Philipps University of MarburgErnst R. Werner - Innsbruck Medical UniversityAaron A. Vogan - McMaster UniversityDawoon Chung - Dartmouth CollegeUlrich Muehlenhoff - Univ Marburg, Inst Zytobiol & Zytopathol, Marburg, GermanyMasashi Kato - Meijo UniversityRobert A. Cramer - Dartmouth CollegeAxel A. Brakhage - Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI)Hubertus Haas - Innsbruck Medical University
- Resource Type
- Journal article
- Publication Details
- The EMBO journal, Vol.33(19), pp.2261-2276
- DOI
- 10.15252/embj.201489468
- PMID
- 25092765
- PMCID
- PMC4232046
- NLM abbreviation
- EMBO J
- ISSN
- 0261-4189
- eISSN
- 1460-2075
- Publisher
- Wiley
- Number of pages
- 16
- Grant note
- BR 1130/14-1 / Deutsche Forschungsgemeinschaft (DFG); German Research Foundation (DFG) HO 2596/1-1 / DFG; German Research Foundation (DFG) NIH R01AI081838 / National Institute of Allergy and Infectious Diseases; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) P21643-B11 / Austrian Science Foundation (FWF); Austrian Science Fund (FWF) R01AI081838 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) T32GM008704 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) I1346-B22 / D-A-CH program "Novel molecular mechanisms of iron sensing and homeostasis in filamentous fungi" (FWF); Austrian Science Fund (FWF)
- Language
- English
- Date published
- 10/01/2014
- Academic Unit
- Stead Family Department of Pediatrics; Infectious Disease (Pediatrics)
- Record Identifier
- 9984354039502771
Metrics
9 Record Views