Heme mediates derepression of Maf recognition element through direct binding to transcription repressor Bach1.
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:
Ogawa
K
K
Laboratory of Environmental Biology, Hokkaido University School of Medicine, Sapporo 060-8638, Japan.
Sun
J
J
Taketani
S
S
Nakajima
O
O
Nishitani
C
C
Sassa
S
S
Hayashi
N
N
Yamamoto
M
M
Shibahara
S
S
Fujita
H
H
Igarashi
K
K
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors; D002645:Chickens; D003001:Cloning, Molecular; D004742:Enhancer Elements, Genetic; D051856:Fanconi Anemia Complementation Group Proteins; D005786:Gene Expression Regulation; D005914:Globins / Q000235:genetics* / Q000378:metabolism; D006418:Heme / Q000378:metabolism*; D006427:Hemin / Q000378:metabolism; D006801:Humans; D050985:MafK Transcription Factor; D008322:Mammals; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014981:Xenopus
C102108:BACH1 protein, human; C486316:Bach1 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; D051856:Fanconi Anemia Complementation Group Proteins; D050985:MafK Transcription Factor; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D006418:Heme; D006427:Hemin; D005914:Globins