Figure 10.

Regulation of DNA binding by heme in vivo. (A) GM02063 cells were transfected with the ho-1 reporter plasmid and indicated Bach1 and MafK expression plasmids. Cells were treated with or without hemin, and binding of Bach1 to the ho-1 E2 enhancer was examined by ChIP. (B) Binding of MafK or Nrf2 to the ho-1 E2 enhancer was examined as in (A). (C) Model describing the regulation of ho-1 or other target genes by Bach1 and heme. Besides MafK, other Maf-related factors may also serve as partners for Bach1. Bach1 occupies MARE enhancers to repress transcription under normal conditions. An increase in heme levels alleviates Bach1-mediated repression through inhibition of its DNA-binding activity and subsequent Crm1-dependent nuclear export, making MAREs available for activating Maf complexes including Nrf2 or p45 NF-E2.