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Updated: Aug 14, 2026

Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
Published on: June 21, 2016
A direct repeat (DR-1) element in the first exon modulates transcription of the preproenkephalin A gene
R M Chan1, M J Stewart, D W Crabb
1Department of Medicine, Indiana University School of Medicine, Indianapolis 46202-5121, USA.
Abstract:
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.
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