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  • The EMBO Journal (2007) 26, 3157 - 3168
  • doi:10.1038/sj.emboj.7601752

Published online: 14 June 2007

Interaction of HapX with the CCAAT-binding complex—a novel mechanism of gene regulation by iron

Peter Hortschansky1,a, Martin Eisendle2,a, Qusai Al-Abdallah1, André D Schmidt1, Sebastian Bergmann1, Marcel Thön1, Olaf Kniemeyer1, Beate Abt2, Birgit Seeber2, Ernst R Werner3, Masashi Kato4, Axel A Brakhage1 and Hubertus Haas2

  1. Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), and Friedrich-Schiller-University Jena, Jena, Germany
  2. Division of Molecular Biology, Biocenter, Innsbruck Medical University, Innsbruck, Austria
  3. Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria
  4. Department of Biological Mechanisms and Functions, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan

Correspondence to:

Hubertus Haas, Division of Molecular Biology, Biocenter, Innsbruck Medical University, Fritz-Pregl-Strasse 3, 6020 Innsbruck, Austria. Tel.: +43 512 9003 70205; Fax: +43 512 9003 73100; E-mail: hubertus.haas@i-med.ac.at

Axel A Brakhage, Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), and Friedrich-Schiller-University Jena, Beutenbergstrasse 11a, 07745 Jena, Germany. Tel.: +49 3641 656601; Fax: +49 3641 656603; E-mail: axel.brakhage@hki-jena.de

aThese authors contributed equally to this work

Received 17 August 2006; Accepted 16 May 2007

Iron homeostasis requires subtle control systems, as iron is both essential and toxic. In Aspergillus nidulans, iron represses iron acquisition via the GATA factor SreA, and induces iron-dependent pathways at the transcriptional level, by a so far unknown mechanism. Here, we demonstrate that iron-dependent pathways (e.g., heme biosynthesis) are repressed during iron-depleted conditions by physical interaction of HapX with the CCAAT-binding core complex (CBC). Proteome analysis identified putative HapX targets. Mutual transcriptional control between hapX and sreA and synthetic lethality resulting from deletion of both regulatory genes indicate a tight interplay of these control systems. Expression of genes encoding CBC subunits was not influenced by iron availability, and their deletion was deleterious during iron-depleted and iron-replete conditions. Expression of hapX was repressed by iron and its deletion was deleterious during iron-depleted conditions only. These data indicate that the CBC has a general role and that HapX function is confined to iron-depleted conditions. Remarkably, CBC-mediated regulation has an inverse impact on the expression of the same gene set in A. nidulans, compared with Saccharomyces cerevisae.

  • Keywords:

    • CCAAT,
    • Hap complex,
    • iron,
    • regulation,
    • siderophore