A direct repeat (DR-1) element in the first exon modulates transcription of the preproenkephalin A gene.

The preproenkephalin A gene is regulated by upstream cis-acting elements which respond to various signals, such as cAMP, calcium, and phorbol esters. An additional regulatory element was detected downstream of the transcription start site of the human preproenkephalin A gene in transfection experiments. The element was localized by DNAse I footprinting and methylation interference assays to a direct repeat (DR-1) element in the first (untranslated) exon. Deletion or mutation of this site reduced transcriptional activity of promoter-reporter constructs by over 50%. Antibodies against COUP-TF beta/ARP-1 and RXR transcription factors altered the pattern seen on electrophoretic mobility shift assays using double-stranded oligonucleotide containing the exon 1 protein binding site. This suggests that the factors that bind this site and modulate transcription of the PPE gene include members of the COUP-TF and retinoid X receptor families.