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

First Author  van Deursen D Year  2009
Journal  Biochim Biophys Acta Volume  1791
Issue  4 Pages  229-37
PubMed ID  19416648 Mgi Jnum  J:148691
Mgi Id  MGI:3846245 Doi  10.1016/j.bbalip.2009.01.017
Citation  van Deursen D, et al. (2009) Upstream Stimulatory Factors 1 and 2 activate the human hepatic lipase promoter via E-box dependent and independent mechanisms. Biochim Biophys Acta 1791(4):229-37
abstractText  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.
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