Activation of the iNOS gene promoter by Brn-3 POU family transcription factors is dependent upon the octamer motif in the promoter.

The promoter of the gene encoding the inducible nitric oxide synthase (iNOS) contains an octamer motif which is of importance for its activation by specific stimuli. We show that in contrast to the promoter of the neuronal nitric oxide synthase gene (nNOS) which is strongly activated by the Oct-2 octamer-binding POU family transcription factor, the iNOS gene is only weakly activated by Oct-2 via its octamer motif. Unlike the nNOS promoter, however, the iNOS promoter is strongly activated by the POU family transcription factors Brn-3a and Brn-3b. This activation is dependent upon the octamer motif in the iNOS promoter and requires the activation domain located within the POU domain of Brn-3a or Brn-3b but not the N-terminal activation domain of Brn-3a. Thus different but related POU proteins play important roles in the regulation of the genes encoding different forms of nitric oxide synthase.