Heme-regulated transcription factor Bach1

Heme is believed to control expression of genes involved in the synthesis of globins and heme itself. However, heme-regulated transcription factor had not been identified in vertebrates. 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. Recently, we found that heme binds specifically to Bach1 and regulates its DNA binding activity. Deletion studies demonstrated that the heme binding region of Bach1 is confined within its C-terminal region that possesses four di-peptide 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 level of intracellular heme inactivates the repressor Bach1, resulting in induction of a host of genes with MAREs.