Functional characterization of the human Huntington's disease gene promoter

Brain Res Mol Brain Res. 2001 Aug 15;92(1-2):85-97. doi: 10.1016/s0169-328x(01)00149-8.


The genetic basis of neurodegeneration in Huntington's disease (HD) has been identified as a (CAG)(>37) repeat expansion in a gene of unknown function. Interestingly, patients with the same expanded (CAG)(n) repeat length may have markedly different ages at onset. Based on experiences in animal models the level of expression might be one of the modifying factors. To gain insight into the regulation of the human HD gene we functionally analyzed 2266 bp of the HD gene promoter region. This region lacks a TATA and a CAAT box, is GCrich, and it has several consensus sequences for SP1, AP-2 and AP-4 binding sites. The stretch between nucleotides -49 and -198 relative to the first ATG is highly conserved between human and rodents and it harbors several potential binding sites for transcription factors. We analyzed deletion mutants fused with the chloramphenicol acetyltransferase (CAT) reporter gene in transfected, huntingtin expressing neuronal (NS20Y) and non-neuronal (CHO) cell lines. Partial deletion of the evolutionarily conserved part of the promoter significantly reduces the activity in both neuronal and non-neuronal cells indicating that the core promoter activity is located between nucleotides -221 and 4, relative to the +1 translation start site. Binding affinities of DNA-protein interactions were defined by electrophoretic mobility shift assays and the protected nucleotide positions were determined by DNase I footprinting.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Animals
  • Base Sequence
  • Binding Sites
  • CHO Cells
  • Chloramphenicol O-Acetyltransferase / biosynthesis
  • Chloramphenicol O-Acetyltransferase / genetics
  • Cricetinae
  • Cricetulus
  • DNA Footprinting
  • Electrophoresis, Polyacrylamide Gel
  • Gene Expression Regulation
  • Genes, Reporter
  • Humans
  • Huntingtin Protein
  • Huntington Disease / epidemiology
  • Huntington Disease / genetics
  • Lac Operon
  • Mice
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics*
  • Neuroblastoma / pathology
  • Neurons / metabolism
  • Nuclear Proteins / genetics*
  • Penetrance
  • Promoter Regions, Genetic*
  • Rats
  • Recombinant Fusion Proteins / biosynthesis
  • Sequence Deletion
  • Species Specificity
  • Transfection
  • Trinucleotide Repeats*
  • Tumor Cells, Cultured
  • beta-Galactosidase / biosynthesis


  • HTT protein, human
  • Htt protein, mouse
  • Htt protein, rat
  • Huntingtin Protein
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Chloramphenicol O-Acetyltransferase
  • beta-Galactosidase