Heme mediates derepression of Maf recognition element through direct binding to transcription repressor Bach1

Kazuhiro Ogawa, Jiying Sun, Shigeru Taketani, Osamu Nakajima, Chiaki Nishitani, Shigeru Sassa, Norio Hayashi, Masayuki Yamamoto, Shigeki Shibahara, Hiroyoshi Fujita, Kazuhiko Igarashi

Research output: Contribution to journalArticlepeer-review

386 Citations (Scopus)

Abstract

Heme controls expression of genes involved in the synthesis of globins and heme. The mammalian transcrip- tion factor Bach1 functions as a repressor of the Maf recognition element (MARE) by forming antagonizing hetero-oligomers with the small Maf family proteins. We show here that heme binds specifically to Bach1 and regulates its DNA-binding activity. Deletion stud- ies demonstrated that a heme-binding region of Bach1 is confined within its C-terminal region that possesses four dipeptide cysteine-proline (CP) motifs. Mutations in all of the CP motifs of Bach1 abolished its interaction with heme. The DNA-binding activity of Bach1 as a MafK hetero-oligomer was markedly inhibited by heme in gel mobility shift assays. The repressor activity of Bach1 was lost upon addition of hemin in transfected cells. These results suggest that increased levels of heme inactivate the repressor Bach1, resulting in induction of a host of genes with MAREs.

Original languageEnglish
Pages (from-to)2835-2843
Number of pages9
JournalEMBO Journal
Volume20
Issue number11
DOIs
Publication statusPublished - 2001 Jun 1

Keywords

  • Heme
  • Maf
  • NF-E2
  • Transcription repression

ASJC Scopus subject areas

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

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