12-O-tetradecanoyl-phorbol-13-acetate down-regulates the Huntingtin promoter at Sp I sites

We have studied the effects of the phorbol ester, 12-O-tetradecanoyl-phorbo l-13-acetate (TPA) on Huntington's disease (HD) gene transcription in neuro nal 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 SpI sites in the region from -213 to -174, relative to the translation start site. The TPA-down-regulating region in HeLa cells wa s mapped to the sequence from -141 to -126. In conclusion, this demonstrate s that HD gene transcription can be down-regulated in vitro in a cell-speci fic manner. NeuroReport 11:3157-3161 (C) 2000 Lippincott Williams & Wilkins .