In vivo phenobarbital treatment increases protein binding to a putative AP-1 site in the CYP2B2 promoter.

Phenobarbital (PB) is a potent inducer of cytochrome P450 enzymes, particularly CYP2B1/2B2. Although the mechanism(s) of PB induction of CYP2B1/2B2 is not fully understood, current research is focusing on the role PB may play in altering the binding of nuclear proteins to critical DNA response elements in the 5'-flanking region of these genes. In this study, rat liver nuclear proteins were analyzed for DNA binding ability using both a general consensus and a CYP2B2 sequence-specific AP-1 oligonucleotide. We demonstrate that in vivo PB treatment enhances protein binding activity to the consensus AP-1 oligonucleotide. Likewise, a putative AP-1 site, identified at -1441 in the CYP2B2 5'-flanking region, also formed a sequence specific DNA/protein complex which was enhanced after PB exposure. These data may support a role of AP-1 in the PB induction mechanism of CYP2B1/2B2.