| First Author | Sun J | Year | 2002 |
| Journal | EMBO J | Volume | 21 |
| Issue | 19 | Pages | 5216-24 |
| PubMed ID | 12356737 | Mgi Jnum | J:100802 |
| Mgi Id | MGI:3589680 | Doi | 10.1093/emboj/cdf516 |
| Citation | Sun J, et al. (2002) Hemoprotein Bach1 regulates enhancer availability of heme oxygenase-1 gene. EMBO J 21(19):5216-24 |
| abstractText | Heme oxygenase-1 (HO-1) protects cells from various insults including oxidative stress. Transcriptional activators, including the Nrf2/Maf heterodimer, have been the focus of studies on the inducible expression of ho-1. Here we show that a heme-binding factor, Bach1, is a critical physiological repressor of ho-1. Bach1 bound to the multiple Maf recognition elements (MAREs) of ho-1 enhancers with MafK in vitro and repressed their activity in vivo, while heme abrogated this repressor function of Bach1 by inhibiting its binding to the ho-1 enhancers. Gene targeting experiments in mice revealed that, in the absence of Bach1, ho-1 became expressed constitutively at high levels in various tissues under normal physiological conditions. By analyzing bach1/nrf2 compound-deficient mice, we documented antagonistic activities of Bach1 and Nrf2 in several tissues. Chromatin immunoprecipitation revealed that small Maf proteins participate in both repression and activation of ho-1. Thus, regulation of ho-1 involves a direct sensing of heme levels by Bach1 (by analogy to lac repressor sensitivity to lactose), generating a simple feedback loop whereby the substrate effects repressor-activator antagonism. |
