Transcription factor AP-2 regulates expression of the dopamine beta-hydroxylase gene.
Expression of the gene encoding the neurotransmitter biosynthetic enzyme dopamine beta-hydroxylase (DBH) is regulated in a tissue-specific pattern, and transcription is influenced by environmental stimuli. Using the promoter proximal region of the rat DBH gene and nuclear extracts from SHSY-5Y neuroblastoma cells, a DNA-protein complex was identified that is competitive with oligonucleotides containing the recognition site of transcription factor AP-2. DNase footprint analysis identified an AP-2 binding site between -136 and -115 of the DBH promoter. Mutation of that AP-2 site results in a sevenfold reduction of basal reporter gene expression, but second messenger-stimulated activity is retained. Cotransfection of an AP-2 expression vector and a DBH promoter-reporter construct into cultured cells results in a sixfold stimulation of reporter gene expression, demonstrating the ability of AP-2 to trans-activate the DBH promoter. These results identify a new regulatory element on the rat DBH gene and suggest that the AP-2 site plays a role in maintaining basal levels of DBH transcription.
Greco
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D
Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland 97201, USA.
Zellmer
E
E
Zhang
Z
Z
Lewis
E
E
D001483:Base Sequence; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000502:physiology*; D004299:Dopamine beta-Hydroxylase / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000235:genetics; D011401:Promoter Regions, Genetic; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D015345:Oligonucleotide Probes; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D004299:Dopamine beta-Hydroxylase