12-O-tetradecanoyl-phorbol-13-acetate down-regulates the Huntingtin promoter at Sp1 sites.
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.
Coles
R
R
Department of Medical Genetics, University of Cambridge, Wellcome Trust Centre for Molecular Mechanisms in Disease, Cambridge Institute for Medical Research, Addenbrooke's Hospital, UK.
Birdsall
M
M
Wyttenbach
A
A
Rubinsztein
D C
DC
D002874:Chromosome Mapping; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D006367:HeLa Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009687:Nuclear Proteins / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects* / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D013755:Tetradecanoylphorbol Acetate