Abstract
We have studied the effects of the phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on Huntington's disease (HD) gene transcription in neuronal and non-neuronal cell lines, to investigate pathways regulating HD gene expression. TPA reduced transcription from the HD gene promoter in SK-N-SH (neuroblastoma) and HeLa cells but not in JEG3 (choriocarcinoma) cells. In SK-N-SH cells, the responsible cis-acting promoter sequences comprise the tandemly duplicated Sp1 sites in the region from -213 to -174, relative to the translation start site. The TPA-down-regulating region in HeLa cells was mapped to the sequence from -141 to -126. In conclusion, this demonstrates that HD gene transcription can be down-regulated in vitro in a cell-specific manner.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Chromosome Mapping
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Down-Regulation / drug effects*
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Down-Regulation / physiology
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Gene Expression Regulation / drug effects*
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Gene Expression Regulation / physiology
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HeLa Cells / cytology
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HeLa Cells / drug effects
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HeLa Cells / metabolism
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Humans
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Huntingtin Protein
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Huntington Disease / genetics*
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Huntington Disease / metabolism
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Huntington Disease / physiopathology
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Nerve Tissue Proteins / drug effects*
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Nerve Tissue Proteins / genetics*
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Nerve Tissue Proteins / metabolism
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Neurons / cytology
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Neurons / drug effects
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Neurons / metabolism
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Nuclear Proteins / drug effects*
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Nuclear Proteins / genetics*
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Nuclear Proteins / metabolism
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Promoter Regions, Genetic / drug effects*
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Promoter Regions, Genetic / physiology
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Tetradecanoylphorbol Acetate / pharmacology*
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Transcription, Genetic / drug effects
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Transcription, Genetic / physiology
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Tumor Cells, Cultured / cytology
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Tumor Cells, Cultured / drug effects
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Tumor Cells, Cultured / metabolism
Substances
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HTT protein, human
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Huntingtin Protein
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Nerve Tissue Proteins
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Nuclear Proteins
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Tetradecanoylphorbol Acetate