title: A direct repeat (DR-1) element in the first exon modulates transcription of the preproenkephalin A gene.
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.
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis 46202-5121, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Chan
authors.forename: M J
authors.initials: MJ
authors.lastname: Stewart
authors.forename: D W
authors.initials: DW
authors.lastname: Crabb
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D002522:Chlorocebus aethiops; D004745:Enkephalins / Q000096:biosynthesis* / Q000235:genetics*; D005091:Exons; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000096:biosynthesis* / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D014158:Transcription, Genetic
chemical_list: D004745:Enkephalins; D011498:Protein Precursors; D011993:Recombinant Fusion Proteins; C033660:preproenkephalin; D015500:Chloramphenicol O-Acetyltransferase