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  • The EMBO Journal (2001) 20, 2835 - 2843
  • doi:10.1093/emboj/20.11.2835

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

Kazuhiro Ogawa1,2, Jiying Sun2,3, Shigeru Taketani4, Osamu Nakajima5, Chiaki Nishitani1, Shigeru Sassa6,7, Norio Hayashi8, Masayuki Yamamoto9, Shigeki Shibahara2, Hiroyoshi Fujita1 and Kazuhiko Igarashi3

  1. Laboratory of Environmental Biology, Hokkaido University School of Medicine, Sapporo 060-8638, Japan
  2. Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai, 980-8575, Japan
  3. Department of Biochemistry, Hiroshima University School of Medicine, Kasumi 1-2-3, Minami-Ku, Hiroshima 734-8551, Japan
  4. Kyoto Institute of Technology, Kyoto 600-8585, Japan
  5. Research Laboratory for Molecular Genetics, Yamagata University, Yamagata 990-9585, Japan
  6. The Rockefeller University, New York, NY 10021, USA
  7. Present address: Yamanouchi Pharmaceutical Co., Ltd, Itabashi-ku, Tokyo 174-0046, Japan
  8. Department of Biochemistry, Tohoku University School of Medicine, Sendai 980-8575, Japan
  9. Center for Tsukuba Advanced Research Alliance and Institute of Basic Medicine, University of Tsukuba, Tsukuba 305-8575, Japan

Correspondence to:

Kazuhiko Igarashi, E-mail: igarak@hiroshima-u.ac.jp

Received 7 February 2001; Accepted 2 April 2001; Revised 2 April 2001

Heme controls expression of genes involved in the synthesis of globins and heme. The mammalian transcription 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 studies 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.

  • Keywords:

    • heme,
    • Maf,
    • NF-E2,
    • transcription repression