Interaction of HapX with the CCAAT-binding complex--a novel mechanism of gene regulation by iron.
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.
Hortschansky
Peter
P
Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), and Friedrich-Schiller-University Jena, Jena, Germany.
Eisendle
Martin
M
Al-Abdallah
Qusai
Q
Schmidt
André D
AD
Bergmann
Sebastian
S
Thön
Marcel
M
Kniemeyer
Olaf
O
Abt
Beate
B
Seeber
Birgit
B
Werner
Ernst R
ER
Kato
Masashi
M
Brakhage
Axel A
AA
Haas
Hubertus
H
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
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