Upstream Stimulatory Factors 1 and 2 activate the human hepatic lipase promoter via E-box dependent and independent mechanisms

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• 作者：Diederik van Deursen ; Marije van Leeuwen ; Sophie Vaulont ; Hans Jansen ; Adrie J.M. Verhoeven
• 关键词：Hepatic lipase ; LIPC ; Promoter polymorphism ; Transcriptional regulation ; Upstream Stimulatory Factor 1 ; Upstream Stimulatory Factor 2
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids
• 出版年：2009
• 出版时间：April 2009
• 年：2009
• 卷：1791
• 期：4
• 页码：229-237
• 全文大小：764 K

文摘

We studied the transcriptional regulation of the HL gene by USF1 and USF2 in HepG2 cells. The transcriptional activity of the HL(− 685/+ 13) promoter construct was increased up to 25-fold by co-transfection with USF1 and USF2. Silencing of USF1 by RNA interference reduced promoter activity by 30–40 % . Chromatin immunoprecipitation assays showed binding of endogenous USF1 and USF2 to the proximal HL promoter region. In gel shift assays, USF1 and USF2 bound to E-boxes at − 307/− 312 and − 510/− 516, and to the TATA-Inr region. Although the − 514C → T substitution abolished in vitro USF binding to the − 510/− 516 E-box, the increase in HL promoter activity by USF1 and USF2 was unaffected. Deletion and mutation analysis of the HL promoter region, and insertion of multiple E-box copies in front of a heterologous promoter, revealed that upregulation by USFs was mainly mediated through the − 307/− 312 E-box and the TATA-Inr region. We conclude that in HepG2 cells USF1 and USF2 regulate transcriptional activity of the HL gene through their binding to the E-box at − 307/− 312 and the TATA-Inr region.