Bach1 is a member of the basic leucine zipper transcription factor family, and 
the Bach1/small Maf heterodimer specifically represses transcriptional activity 
directed by the Maf recognition element (MARE). Because Bach1 is a repressor of 
the oxidative stress response, we examined the function(s) of Bach1 in 
keratinocytes subjected to oxidative stress. Oxidative stress induced by 
H(2)O(2) led to an increase in MARE activity and expression of heme oxygenase-1 
(HO-1), an inducible antioxidant defense enzyme. Bach1 depletion by small 
interfering RNAs or by deletion of Bach1 enhanced HO-1 expression in the absence 
of H(2)O(2), indicating that Bach1 is a critical repressor of HO-1 in 
keratinocytes. Although Bach1-deficient or -reduced keratinocytes expressed 
higher levels of HO-1 than control cells in response to H(2)O(2), Bach1 
down-regulation did not attenuate the production of reactive oxygen species by 
H(2)O(2). In contrast, Bach1 overexpression abolished HO-1 induction by 
H(2)O(2), which led to increased reactive oxygen species accumulation. HO-1 was 
induced during keratinocyte differentiation, but MARE activity did not change 
during differentiation. Furthermore, Bach1 overexpression did not inhibit 
differentiation-associated induction of HO-1 expression, suggesting that HO-1 
induction in differentiation is independent of Bach1. Thus, in response to 
oxidative stress, Bach1 regulates the oxidation state through the negative 
control of HO-1 expression prior to terminal keratinocyte differentiation. 
However, Bach1-mediated repression is negated during keratinocyte 
differentiation.