TRANSCRIPTIONAL ACTIVATION OF THE HUMAN ROD CGMP-PHOSPHODIESTERASE BETA-SUBUNIT GENE IS MEDIATED BY AN UPSTREAM AP-1 ELEMENT

During photoactivation retinal cGMP-phosphodiesterase (PDE) mediates s ignal transduction in the photoreceptor outer segments. Mutations in t he beta-subunit gene of rod-specific PDE (beta-PDE) have been associat ed with inherited retinal degeneration in a number of species, includi ng human. Here we have investigated the proximal upstream sequences th at participate in transcriptional activation of this gene. Transient t ransfections demonstrated that the sequence from -72 to +53 bp contain ed sufficient information to direct high levels of gene expression in cells of retinal origin. Deletion or mutagenesis of an AP-1 motif pres ent in this region caused 90-95% reduction in reporter gene expression . By gel mobility shift assay we demonstrated,specific interactions be tween putative nuclear transcription factors and this AP-1 element. Th ese findings indicate that the proximal AP-1 site in the human beta-PD E promoter is functionally relevant and necessary for transcriptional activation of this gene.