Heme oxygenase 1 (HO-1) catalyzes heme breakdown, eventually releasing iron, 
carbon monoxide, and bilirubin IXalpha. HO-1 is induced by its substrate heme 
and various environmental factors, which represents a protective response 
against oxidative stresses. Here we show that hypoxia represses HO-1 expression 
in three human cell types but induces it in rat, bovine, and monkey cells, 
indicating the inter-species difference in the hypoxic regulation of HO-1 
expression. The hypoxia-mediated repression of HO-1 expression is consistently 
associated with the induction of Bach1, a heme-regulated transcriptional 
repressor, in human cells. Bach1 is a basic leucine zipper protein, forming a 
heterodimer with a small Maf protein. Expression of HO-1 was also reduced in 
human cells when exposed to interferon-gamma or an iron chelator 
desferrioxamine, each of which induced Bach1 expression. In contrast, induction 
of HO-1 expression by CoCl(2) is associated with reduced expression of Bach1 
mRNA. Thus, expression of HO-1 and Bach1 is inversely regulated. We have 
identified a Maf recognition element in the human HO-1 gene that is required for 
repression of a reporter gene by hypoxia and targeted by Bach1. Therefore, Bach1 
functions as a hypoxia-inducible repressor for the HO-1 gene, thereby 
contributing to fine-tuning of oxygen homeostasis in human cells.