Heme oxygenase-1 (HO-1), the rate-limiting enzyme of heme degradation and 
antioxidant defense protein, is induced in the lungs of animals exposed to 
hyperoxia. However, high levels of HO-1 expression may be deleterious, thus 
necessitating tight regulation. Previous reports show maturational differences 
in rat HO-1 regulation in hyperoxia, as newborns do not up-regulate HO-1mRNA 
compared with adults. To better understand the differential response of lung 
HO-1 to hyperoxia, we exposed newborn and adult mice to >95% oxygen. The newborn 
lungs had reduced HO-1 mRNA induction compared with adults and newborn 
transgenic mice over-expressing luciferase driven by the 15 kb HO-1 promoter 
(HO-1/Luc Tg) had less increased light emission in hyperoxia compared with 
adults. Compared with adults, levels of the repressor of HO-1 transcription, 
Bach1, were higher in the neonatal lung as was nuclear protein-DNA binding to 
the antioxidant response element (ARE) from HO-1. Furthermore, at baseline and 
in hyperoxia, chromatin immunoprecipitation (ChIP) revealed increased Bach1 
binding to the HO-1 distal enhancers (DEs) in the neonates compared with adults. 
These data suggest that elevated levels of Bach1 may help to limit HO-1 
induction in the newborn at baseline and in response to oxidative stress.