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 elemen ts which respond to various signals, such as cAMP, calcium, and phorbo l esters. An additional regulatory element was detected downstream of the transcription start site of the human preproenkephalin A gene in t ransfection experiments. The element was localized by DNAse I footprin ting and methylation interference assays to a direct repeat (DR-I) ele ment in the first (untranslated) exon. Deletion or mutation of this si te 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 as says using double-stranded oligonucleotide containing the exon 1 prote in binding site. This suggests that the factors that bind this site an d modulate transcription of the PPE gene include members of the COUP-T F and retinoid X receptor families.