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Transcription Factor AP‐2 Regulates Expression of the Dopamine β‐Hydroxylase Gene
Author(s) -
Greco Dominique,
Zellmer Eustacia,
Zhang Zheng,
Lewis Elaine
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.65020510.x
Subject(s) - transcription factor , gene , dopamine , gene expression , biology , genetics , microbiology and biotechnology , neuroscience
Expression of the gene encoding the neurotransmitter biosynthetic enzyme dopamine β‐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.