Intracellular heme is a redox active molecule that can be detrimental to cells 
at high concentrations or under oxidizing conditions. To prevent accumulation, 
the inducible enzyme heme oxygenase-1 (HMOX1) catalyzes degradation of heme. In 
the absence of elevated intracellular heme or oxidative stress, the basic region 
leucine zipper transcriptional regulator BACH1 binds HMOX1 antioxidant response 
elements and represses transcription. Conversely, increased intracellular heme 
or sulfhydryl oxidation inactivate BACH1, permitting transcriptional induction 
of HMOX1. Here, we investigate the effect of BACH1 inactivation on the induction 
of HMOX1 and as a mechanism for broader gene induction. We show that BACH1 is 
inactivated at low micromolar arsenite concentrations and that BACH1 
inactivation is necessary and sufficient for transcriptional induction of HMOX1. 
Because BACH1 is thought to interact with antioxidant response element motifs, 
we further examined the role of BACH1 as a regulator of inducible antioxidant 
gene expression by assessing the global profile of gene expression following 
BACH1 knockdown using small interfering RNA. The loss of BACH1 function in human 
keratinocytes results almost exclusively in HMOX1 induction, suggesting that 
BACH1 may function as a rheostat regulating levels of intracellular free heme.