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The Janus transcription factor HapX controls fungal adaptation to both iron starvation and iron excess
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 demonstrat...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BlackWell Publishing Ltd
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4232046/ https://www.ncbi.nlm.nih.gov/pubmed/25092765 http://dx.doi.org/10.15252/embj.201489468 |
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author | Gsaller, Fabio Hortschansky, Peter Beattie, Sarah R Klammer, Veronika Tuppatsch, Katja Lechner, Beatrix E Rietzschel, Nicole Werner, Ernst R Vogan, Aaron A Chung, Dawoon Mühlenhoff, Ulrich Kato, Masashi Cramer, Robert A Brakhage, Axel A Haas, Hubertus |
author_facet | Gsaller, Fabio Hortschansky, Peter Beattie, Sarah R Klammer, Veronika Tuppatsch, Katja Lechner, Beatrix E Rietzschel, Nicole Werner, Ernst R Vogan, Aaron A Chung, Dawoon Mühlenhoff, Ulrich Kato, Masashi Cramer, Robert A Brakhage, Axel A Haas, Hubertus |
author_sort | Gsaller, Fabio |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4232046 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BlackWell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-42320462014-12-15 The Janus transcription factor HapX controls fungal adaptation to both iron starvation and iron excess Gsaller, Fabio Hortschansky, Peter Beattie, Sarah R Klammer, Veronika Tuppatsch, Katja Lechner, Beatrix E Rietzschel, Nicole Werner, Ernst R Vogan, Aaron A Chung, Dawoon Mühlenhoff, Ulrich Kato, Masashi Cramer, Robert A Brakhage, Axel A Haas, Hubertus EMBO J Articles 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. BlackWell Publishing Ltd 2014-10-01 2014-08-04 /pmc/articles/PMC4232046/ /pubmed/25092765 http://dx.doi.org/10.15252/embj.201489468 Text en © 2014 The Authors. Published under the terms of the CC BY 4.0 license http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles Gsaller, Fabio Hortschansky, Peter Beattie, Sarah R Klammer, Veronika Tuppatsch, Katja Lechner, Beatrix E Rietzschel, Nicole Werner, Ernst R Vogan, Aaron A Chung, Dawoon Mühlenhoff, Ulrich Kato, Masashi Cramer, Robert A Brakhage, Axel A Haas, Hubertus The Janus transcription factor HapX controls fungal adaptation to both iron starvation and iron excess |
title | The Janus transcription factor HapX controls fungal adaptation to both iron starvation and iron excess |
title_full | The Janus transcription factor HapX controls fungal adaptation to both iron starvation and iron excess |
title_fullStr | The Janus transcription factor HapX controls fungal adaptation to both iron starvation and iron excess |
title_full_unstemmed | The Janus transcription factor HapX controls fungal adaptation to both iron starvation and iron excess |
title_short | The Janus transcription factor HapX controls fungal adaptation to both iron starvation and iron excess |
title_sort | janus transcription factor hapx controls fungal adaptation to both iron starvation and iron excess |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4232046/ https://www.ncbi.nlm.nih.gov/pubmed/25092765 http://dx.doi.org/10.15252/embj.201489468 |
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