Transcription factor AP-2 regulates expression of the dopamine beta-hydroxylase gene

J Neurochem. 1995 Aug;65(2):510-6. doi: 10.1046/j.1471-4159.1995.65020510.x.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Binding Sites
  • DNA-Binding Proteins / physiology*
  • Dopamine beta-Hydroxylase / genetics*
  • Gene Expression Regulation*
  • Humans
  • Molecular Sequence Data
  • Oligonucleotide Probes / genetics
  • Promoter Regions, Genetic
  • Transcription Factor AP-2
  • Transcription Factors / physiology*
  • Transcription, Genetic
  • Tumor Cells, Cultured

Substances

  • DNA-Binding Proteins
  • Oligonucleotide Probes
  • Transcription Factor AP-2
  • Transcription Factors
  • Dopamine beta-Hydroxylase