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.