Heme regulates gene expression by triggering Crm1-dependent nuclear export of Bach1

Hiroshi Suzuki, Satoshi Tashiro, Shusuke Hira, Jiying Sun, Chikara Yamazaki, Yukari Zenke, Masao Ikeda-Saito, Minoru Yoshida, Kazuhiko Igarashi

Research output: Contribution to journalArticlepeer-review

141 Citations (Scopus)

Abstract

Bach1 is a transcriptional represser of heme oxygenase-1 and β-globin genes, both of which are known to be transcriptionally induced by heme. To test the hypothesis that heme regulates the activity of Bach1, we expressed wild type and mutated versions of Bach1 together with or without its heterodimer partner MafK in human 293T and GM02063 cells and examined their subcellular localization. Inhibition of heme synthesis enhanced the nuclear accumulation of Bach1, whereas treating cells with hemin resulted in nuclear exclusion of Bach1. While the cadmium-inducible nuclear export signal (NES) of Bach1 was dispensable for the heme response, a region containing two of the heme-binding motifs was found to be critical for the heme-induced nuclear exclusion. This region functioned as a heme-regulated NES dependent on the exporter Crm1. These results extend the regulatory roles for heme in protein sorting, and suggest that Bach1 transduces metabolic activity into gene expression.

Original languageEnglish
Pages (from-to)2544-2553
Number of pages10
JournalEMBO Journal
Volume23
Issue number13
DOIs
Publication statusPublished - 2004 Jul 7

Keywords

  • Globin
  • Heme
  • Heme oxygenase
  • Maf
  • Oxidative stress

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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