Journal
EMBO JOURNAL
Volume 20, Issue 11, Pages 2835-2843Publisher
WILEY
DOI: 10.1093/emboj/20.11.2835
Keywords
heme; Maf; NF-E2; transcription repression
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Funding
- NIDDK NIH HHS [DK-32890] Funding Source: Medline
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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-hinding 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.
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