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The fungal CCAAT-binding complex and HapX display highly variable but evolutionary conserved synergetic promoter-specific DNA recognition
To sustain iron homeostasis, microorganisms have evolved fine-tuned mechanisms for uptake, storage and detoxification of the essential metal iron. In the human pathogen Aspergillus fumigatus, the fungal-specific bZIP-type transcription factor HapX coordinates adaption to both iron starvation and iro...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144946/ https://www.ncbi.nlm.nih.gov/pubmed/32086516 http://dx.doi.org/10.1093/nar/gkaa109 |
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author | Furukawa, Takanori Scheven, Mareike Thea Misslinger, Matthias Zhao, Can Hoefgen, Sandra Gsaller, Fabio Lau, Jeffrey Jöchl, Christoph Donaldson, Ian Valiante, Vito Brakhage, Axel A Bromley, Michael J Haas, Hubertus Hortschansky, Peter |
author_facet | Furukawa, Takanori Scheven, Mareike Thea Misslinger, Matthias Zhao, Can Hoefgen, Sandra Gsaller, Fabio Lau, Jeffrey Jöchl, Christoph Donaldson, Ian Valiante, Vito Brakhage, Axel A Bromley, Michael J Haas, Hubertus Hortschansky, Peter |
author_sort | Furukawa, Takanori |
collection | PubMed |
description | To sustain iron homeostasis, microorganisms have evolved fine-tuned mechanisms for uptake, storage and detoxification of the essential metal iron. In the human pathogen Aspergillus fumigatus, the fungal-specific bZIP-type transcription factor HapX coordinates adaption to both iron starvation and iron excess and is thereby crucial for virulence. Previous studies indicated that a HapX homodimer interacts with the CCAAT-binding complex (CBC) to cooperatively bind bipartite DNA motifs; however, the mode of HapX-DNA recognition had not been resolved. Here, combination of in vivo (genetics and ChIP-seq), in vitro (surface plasmon resonance) and phylogenetic analyses identified an astonishing plasticity of CBC:HapX:DNA interaction. DNA motifs recognized by the CBC:HapX protein complex comprise a bipartite DNA binding site 5′-CSAATN(12)RWT-3′ and an additional 5′-TKAN-3′ motif positioned 11–23 bp downstream of the CCAAT motif, i.e. occasionally overlapping the 3′-end of the bipartite binding site. Phylogenetic comparison taking advantage of 20 resolved Aspergillus species genomes revealed that DNA recognition by the CBC:HapX complex shows promoter-specific cross-species conservation rather than regulon-specific conservation. Moreover, we show that CBC:HapX interaction is absolutely required for all known functions of HapX. The plasticity of the CBC:HapX:DNA interaction permits fine tuning of CBC:HapX binding specificities that could support adaptation of pathogens to their host niches. |
format | Online Article Text |
id | pubmed-7144946 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-71449462020-04-13 The fungal CCAAT-binding complex and HapX display highly variable but evolutionary conserved synergetic promoter-specific DNA recognition Furukawa, Takanori Scheven, Mareike Thea Misslinger, Matthias Zhao, Can Hoefgen, Sandra Gsaller, Fabio Lau, Jeffrey Jöchl, Christoph Donaldson, Ian Valiante, Vito Brakhage, Axel A Bromley, Michael J Haas, Hubertus Hortschansky, Peter Nucleic Acids Res Gene regulation, Chromatin and Epigenetics To sustain iron homeostasis, microorganisms have evolved fine-tuned mechanisms for uptake, storage and detoxification of the essential metal iron. In the human pathogen Aspergillus fumigatus, the fungal-specific bZIP-type transcription factor HapX coordinates adaption to both iron starvation and iron excess and is thereby crucial for virulence. Previous studies indicated that a HapX homodimer interacts with the CCAAT-binding complex (CBC) to cooperatively bind bipartite DNA motifs; however, the mode of HapX-DNA recognition had not been resolved. Here, combination of in vivo (genetics and ChIP-seq), in vitro (surface plasmon resonance) and phylogenetic analyses identified an astonishing plasticity of CBC:HapX:DNA interaction. DNA motifs recognized by the CBC:HapX protein complex comprise a bipartite DNA binding site 5′-CSAATN(12)RWT-3′ and an additional 5′-TKAN-3′ motif positioned 11–23 bp downstream of the CCAAT motif, i.e. occasionally overlapping the 3′-end of the bipartite binding site. Phylogenetic comparison taking advantage of 20 resolved Aspergillus species genomes revealed that DNA recognition by the CBC:HapX complex shows promoter-specific cross-species conservation rather than regulon-specific conservation. Moreover, we show that CBC:HapX interaction is absolutely required for all known functions of HapX. The plasticity of the CBC:HapX:DNA interaction permits fine tuning of CBC:HapX binding specificities that could support adaptation of pathogens to their host niches. Oxford University Press 2020-04-17 2020-02-22 /pmc/articles/PMC7144946/ /pubmed/32086516 http://dx.doi.org/10.1093/nar/gkaa109 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Gene regulation, Chromatin and Epigenetics Furukawa, Takanori Scheven, Mareike Thea Misslinger, Matthias Zhao, Can Hoefgen, Sandra Gsaller, Fabio Lau, Jeffrey Jöchl, Christoph Donaldson, Ian Valiante, Vito Brakhage, Axel A Bromley, Michael J Haas, Hubertus Hortschansky, Peter The fungal CCAAT-binding complex and HapX display highly variable but evolutionary conserved synergetic promoter-specific DNA recognition |
title | The fungal CCAAT-binding complex and HapX display highly variable but evolutionary conserved synergetic promoter-specific DNA recognition |
title_full | The fungal CCAAT-binding complex and HapX display highly variable but evolutionary conserved synergetic promoter-specific DNA recognition |
title_fullStr | The fungal CCAAT-binding complex and HapX display highly variable but evolutionary conserved synergetic promoter-specific DNA recognition |
title_full_unstemmed | The fungal CCAAT-binding complex and HapX display highly variable but evolutionary conserved synergetic promoter-specific DNA recognition |
title_short | The fungal CCAAT-binding complex and HapX display highly variable but evolutionary conserved synergetic promoter-specific DNA recognition |
title_sort | fungal ccaat-binding complex and hapx display highly variable but evolutionary conserved synergetic promoter-specific dna recognition |
topic | Gene regulation, Chromatin and Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144946/ https://www.ncbi.nlm.nih.gov/pubmed/32086516 http://dx.doi.org/10.1093/nar/gkaa109 |
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