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Heme Mediates Derepression of Maf Recognition Element Through Direct Binding to Transcription Repressor Bach1

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Journal EMBO J
Date 2001 Jun 2
PMID 11387216
Citations 220
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Abstract

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:

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References
1.
Yoshida C, Tokumasu F, Hohmura K, Bungert J, Hayashi N, Nagasawa T . Long range interaction of cis-DNA elements mediated by architectural transcription factor Bach1. Genes Cells. 2000; 4(11):643-55. DOI: 10.1046/j.1365-2443.1999.00291.x. View

2.
Alam J, Stewart D, Touchard C, Boinapally S, Choi A, Cook J . Nrf2, a Cap'n'Collar transcription factor, regulates induction of the heme oxygenase-1 gene. J Biol Chem. 1999; 274(37):26071-8. DOI: 10.1074/jbc.274.37.26071. View

3.
Chefalo P, Hussain Z, Hahn J, Uma S, Matts R, Chen J . Two heme-binding domains of heme-regulated eukaryotic initiation factor-2alpha kinase. N terminus and kinase insertion. J Biol Chem. 2000; 275(7):5171-8. DOI: 10.1074/jbc.275.7.5171. View

4.
Kramer M, Gunaratne P, Ferreira G . Transcriptional regulation of the murine erythroid-specific 5-aminolevulinate synthase gene. Gene. 2000; 247(1-2):153-66. DOI: 10.1016/s0378-1119(00)00103-7. View

5.
Ishii T, Itoh K, Takahashi S, Sato H, Yanagawa T, Katoh Y . Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages. J Biol Chem. 2000; 275(21):16023-9. DOI: 10.1074/jbc.275.21.16023. View