12-O-十四烷酰佛波醇-13-乙酸酯在Sp1位点下调亨廷顿蛋白启动子。

12-O-tetradecanoyl-phorbol-13-acetate down-regulates the Huntingtin promoter at Sp1 sites.

作者信息

Coles R, Birdsall M, Wyttenbach A, Rubinsztein D C

机构信息

Department of Medical Genetics, University of Cambridge, Wellcome Trust Centre for Molecular Mechanisms in Disease, Cambridge Institute for Medical Research, Addenbrooke's Hospital, UK.

出版信息

Neuroreport. 2000 Sep 28;11(14):3157-61. doi: 10.1097/00001756-200009280-00023.

DOI:10.1097/00001756-200009280-00023

PMID:11043541

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.

摘要

我们研究了佛波酯12 - O -十四烷酰佛波醇- 13 -乙酸酯（TPA）对神经元和非神经元细胞系中亨廷顿舞蹈病（HD）基因转录的影响，以探究调节HD基因表达的途径。TPA降低了SK - N - SH（神经母细胞瘤）和HeLa细胞中HD基因启动子的转录，但在JEG3（绒毛膜癌）细胞中未降低。在SK - N - SH细胞中，起作用的顺式作用启动子序列包括相对于翻译起始位点从- 213至- 174区域内串联重复的Sp1位点。HeLa细胞中TPA下调区域定位于从- 141至- 126的序列。总之，这表明HD基因转录在体外可通过细胞特异性方式被下调。