Bach1, a heme-dependent transcription factor, reveals presence of multiple heme binding sites with distinct coordination structure

Shusuke Hira, Takeshi Tomita, Toshitaka Matsui, Kazuhiko Igarashi, Masao Ikeda-Saito

Research output: Contribution to journalReview articlepeer-review

70 Citations (Scopus)

Abstract

The mammalian transcription factor Bach1 functions as a repressor of the enhancers of heme oxygenase-1 (HO-1) gene (Hmox-1) by forming heterodimers with the small Maf proteins such as MafK. The transcription of Hmox-1 is regulated by the substrate of HO-1, heme. Heme induces expression of Hmox-1 in part by inhibiting the binding of Bach1 to the enhancers and inducing the nuclear export of Bach1. A dipeptide motif of cysteine and proline (CP motif) in Bach1 is essential for the heme-mediated regulation. In this study, we show that five molecules of heme bind to Bach1 by the heme-titration assay. The Bach1-heme complex exhibits an absorption spectrum with a major Soret peak at 371 nm and Raman band at 343 cm-1 in high amounts of heme and a spectrum containing the major Soret peak at 423 nm at low heme concentrations. The spectroscopic characterization indicates that Bach1 has two kinds of heme-binding sites with different coordination structures. Mutagenesis studies have established that four molecules of heme bind to the cysteine residues of four CP motifs in the C terminus of Bach1. These results raise the possibility that two separated activities of Bach1, DNA-binding and nuclear export, are regulated by heme binding at the different CP motifs of Bach1 respectively, but not by cooperative heme-binding.

Original languageEnglish
Pages (from-to)542-551
Number of pages10
JournalIUBMB Life
Volume59
Issue number8-9
DOIs
Publication statusPublished - 2007

Keywords

  • Heme binding mode
  • Heme mediated regulation
  • Heme oxygenase
  • Spectroscopic characterization
  • Transcription factor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Clinical Biochemistry
  • Cell Biology

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