title: Interaction of HapX with the CCAAT-binding complex--a novel mechanism of gene regulation by iron.
abstract: 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.
authors.affiliation: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), and Friedrich-Schiller-University Jena, Jena, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hortschansky
authors.forename: Martin
authors.initials: M
authors.lastname: Eisendle
authors.forename: Qusai
authors.initials: Q
authors.lastname: Al-Abdallah
authors.forename: André D
authors.initials: AD
authors.lastname: Schmidt
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bergmann
authors.forename: Marcel
authors.initials: M
authors.lastname: Thön
authors.forename: Olaf
authors.initials: O
authors.lastname: Kniemeyer
authors.forename: Beate
authors.initials: B
authors.lastname: Abt
authors.forename: Birgit
authors.initials: B
authors.lastname: Seeber
authors.forename: Ernst R
authors.initials: ER
authors.lastname: Werner
authors.forename: Masashi
authors.initials: M
authors.lastname: Kato
authors.forename: Axel A
authors.initials: AA
authors.lastname: Brakhage
authors.forename: Hubertus
authors.initials: H
authors.lastname: Haas
mesh_terms: D001233:Aspergillus nidulans / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D023081:CCAAT-Binding Factor / Q000235:genetics / Q000378:metabolism*; D004271:DNA, Fungal / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D050980:GATA Transcription Factors / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects*; D005804:Genes, Lethal / Q000235:genetics; D006418:Heme / Q000378:metabolism; D007501:Iron / Q000494:pharmacology*; D015394:Molecular Structure; D011485:Protein Binding; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D011524:Protoporphyrins / Q000378:metabolism; D018085:Regulon / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D017262:Siderophores / Q000096:biosynthesis / Q000737:chemistry; D015398:Signal Transduction; D020349:Surface Plasmon Resonance
chemical_list: D001426:Bacterial Proteins; D023081:CCAAT-Binding Factor; D004271:DNA, Fungal; D005656:Fungal Proteins; D050980:GATA Transcription Factors; D021122:Protein Subunits; D011524:Protoporphyrins; D012097:Repressor Proteins; C117706:SREA protein, Aspergillus nidulans; D017262:Siderophores; C035832:hook protein, bacterial flagellum; D006418:Heme; C028025:protoporphyrin IX; D007501:Iron