GENETICS OF NERVOUS SYSTEM DISEASES12-O-Tetradecanoyl-phorbol-13-acetate down-regulates the Huntingtin promoter at Spl sitesColes, Rhian1,2; Birdsall, Michelle1; Wyttenbach, Andreas1; Rubinsztein, David C.1,3Author Information 1Department of Medical Genetics, University of Cambridge, Wellcome Trust Centre for Molecular Mechanisms in Disease, Cambridge Institute for Medical Research, Wellcome/MRC Building, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2XY, UK 2Department of Pathology, University of Cambridge, Wellcome Trust Centre for Molecular Mechanisms in Disease, Cambridge Institute for Medical Research, Wellcome/MRC Building, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2XY, UK 3Corresponding Author: David C. Rubinsztein Acknowledgements: R.C. is grateful for a Wellcome Trust Prize Studentship, D.C.R. is a Glaxo Wellcome Research Fellow. A.W. is grateful to the Swiss National Science Foundation for a post-doctoral fellowship. We thank the Violet Richards Charity and The Isaac Newton Trust for support. Received 27 June 2000; accepted 14 July 2000 NeuroReport: September 28, 2000 - Volume 11 - Issue 14 - p 3157-3161 Buy 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 SKN-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 Spl 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. © 2000 Lippincott Williams & Wilkins, Inc.