Functional analysis of the Huntington's disease (HD) gene promoter.
The basis for the highly specific neuronal vulnerability seen in Huntington's disease (HD) has not been determined. Recent studies have demonstrated that variation in HD protein expression occurs in the striatum, with affected regions showing increased HD immunoreactivity. Experiments in HD and SCA1 transgenic mice suggest a correlation between phenotypic severity and expression of the mutant transgene. To gain insights into control of HD gene expression, and to investigate the possibility of cell-cell differences in transcription, we have analysed the 5' upstream region of the HD gene in a neuronal (SK-N-SH) and a non-neuronal (JEG3) cell line. Reporter gene assays demonstrated the presence of a key positive-acting region apparently arising from two Sp1 sites in a tandem repeat acting synergistically. This site is polymorphic, and a single Sp1 site is associated with reduced levels of transcription. These experiments also reveal differences in control of expression between neuronal and non-neuronal cell lines.
Coles
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Department of Medical Genetics, University of Cambridge, Box 158, Addenbrooke's NHS Trust, Hills Road, Cambridge CB2 2QQ, UK.
Caswell
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Rubinsztein
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D001665:Binding Sites / Q000235:genetics; D002822:Choriocarcinoma; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics*; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009447:Neuroblastoma; D009687:Nuclear Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors