Interaction of HapX With the CCAAT-binding Complex--A Novel Mechanism of Gene Regulation by Iron

EMBO J. 2007 Jul 11;26(13):3157-68. doi: 10.1038/sj.emboj.7601752. Epub 2007 Jun 14.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspergillus nidulans / drug effects*
  • Aspergillus nidulans / genetics*
  • Aspergillus nidulans / metabolism
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • CCAAT-Binding Factor / genetics
  • CCAAT-Binding Factor / metabolism*
  • DNA, Fungal / genetics
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • GATA Transcription Factors / genetics
  • GATA Transcription Factors / metabolism
  • Gene Deletion
  • Gene Expression Regulation, Fungal / drug effects*
  • Genes, Lethal / genetics
  • Heme / metabolism
  • Iron / pharmacology*
  • Molecular Structure
  • Protein Binding
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Protoporphyrins / metabolism
  • Regulon / genetics
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Siderophores / biosynthesis
  • Siderophores / chemistry
  • Signal Transduction
  • Surface Plasmon Resonance


  • Bacterial Proteins
  • CCAAT-Binding Factor
  • DNA, Fungal
  • Fungal Proteins
  • GATA Transcription Factors
  • Protein Subunits
  • Protoporphyrins
  • Repressor Proteins
  • SREA protein, Aspergillus nidulans
  • Siderophores
  • hook protein, bacterial flagellum
  • Heme
  • protoporphyrin IX
  • Iron