期刊
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION
卷 1759, 期 7, 页码 367-377出版社
ELSEVIER
DOI: 10.1016/j.bbaexp.2006.06.005
关键词
WFS1; Wolfram syndrome; minimal promoter; Sp1; Sp3; CCAAT; ERSE
Wolfram Syndrome (DIDMOAD) is an autosomal recessive disorder characterised by insulin deficient diabetes mellitus and neurodegeneration. Mutations in a novel gene, WFS1, were found in nearly all patients and segregated with the disease. The WFS1 gene is expressed in all tissue types studied and the 890aa protein product is localised to the endoplasmic reticulum (ER). In this study, we used a combination of reporter assays and in vitro and in vivo transcription factor binding assays to analyse the regulation of expression of the human WFS1 gene in neuronal derived cells. A single transcription start site was mapped and a minimal promoter identified within 25 bp upstream of this site. This minimal promoter contains two DNA binding motifs (GC boxes) for the transcription factors Sp1/3/4 and binding of both Sp1 and Sp3 was demonstrated at both motifs in vitro and in vivo. The presence of intact GC boxes is essential for minimal promoter action. Thus, transcription factors of the Sp family are important regulators of the WFS1 promoter. A further up-regulating control region was identified containing three CCAAT box binding motifs; all demonstrated a reduction in expression after mutation. One CCAAT box represented part of a predicted ER stress response element. (c) 2006 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据