Novel regulatory sites of the human heme oxygenase-1 promoter region.

Heme oxygenase is the rate-limiting enzyme in heme catabolism, the activity of which is induced by several agents including its substrate heme, u.v. radiation and other oxidant injurious conditions. Its biological function is to provide a specific regulatory mechanism for control of the level of many heme proteins. Using a computer-assisted approach, we examined the presence of different regulatory elements on the human heme oxygenase-1 promoter region which could possibly be involved in its regulation. We identified several NFkB and AP-2-like binding sites in the 5' untranslated region of the human heme oxygenase gene. DNase I footprint analysis confirmed the presence of these two important transcriptional sites. This study is the first to reveal the presence of NFkB and AP-2 binding sites in the heme oxygenase-1 promoter region and thus suggests a role for these transcriptional factors in the regulation of heme oxygenase-1 expression, a stress and heat shock protein, under injury conditions.