Winged helix hepatocyte nuclear factor 3 and POU-domain protein brn-2/N-oct-3 bind overlapping sites on the neuronal promoter of human aromatic L-amino acid decarboxylase gene

Brain Res Mol Brain Res. 1998 May;56(1-2):227-37. doi: 10.1016/s0169-328x(98)00048-5.

Abstract

The neuronal promoter of human aromatic l-amino acid decarboxylase gene has been analysed to elucidate the mechanisms of neuron type-specific expression. The (-560/+92) promoter segment was sufficient to direct luciferase expression at a higher level in SK-N-BE neuroblastoma cells, than in CHP126 neuroepithelia, HepG2 hepatoma or SK-Hep1 epithelioma cells. Deletions experiments showed that this segment contained a neuronal-specific (element T1) and a SK-N-BE-specific (element N1) cis-activating sequences. Element T1 (-72/-36) bound Sp1 and NF-Y proteins, and unidentified neuronal-specific factors. Element N1 (-102/-72) bound cell-specific factors, identified as HNF-3, N-Oct-3/Brn-2 and N-Oct-2. HNF-3 proteins recognized the sequence TCAGTAAATA that matches the consensus motif. Oct-1, N-Oct-2 and N-Oct-3 bound the AAATAATGC sequence that overlaps the HNF-3 binding site. In addition, we show that the HNF-3 binding sites from aldolase C and HNF-3beta gene promoters also bind N-Oct-2 and N-Oct-3 proteins. These data suggest a functional interplay of winged helix/forkhead and POU-domain transcription factors on a variety of neuronal gene promoters.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aromatic-L-Amino-Acid Decarboxylases / genetics*
  • Binding Sites / genetics
  • COS Cells
  • DNA-Binding Proteins / metabolism*
  • DNA-Binding Proteins / physiology
  • Helix-Loop-Helix Motifs*
  • Hepatocyte Nuclear Factor 3-alpha
  • Hepatocyte Nuclear Factor 3-beta
  • Hepatocyte Nuclear Factor 3-gamma
  • Homeodomain Proteins
  • Humans
  • Neurons / cytology
  • Neurons / metabolism*
  • Nuclear Proteins / metabolism*
  • Nuclear Proteins / physiology
  • POU Domain Factors
  • Promoter Regions, Genetic / genetics*
  • Transcription Factors / metabolism*
  • Transcription Factors / physiology
  • Tumor Cells, Cultured

Substances

  • DNA-Binding Proteins
  • FOXA1 protein, human
  • FOXA2 protein, human
  • FOXA3 protein, human
  • Hepatocyte Nuclear Factor 3-alpha
  • Homeodomain Proteins
  • Nuclear Proteins
  • POU Domain Factors
  • Transcription Factors
  • transcription factor Brn-2
  • Hepatocyte Nuclear Factor 3-gamma
  • Hepatocyte Nuclear Factor 3-beta
  • Aromatic-L-Amino-Acid Decarboxylases