Document Detail

Upstream Stimulatory Factors 1 and 2 activate the human hepatic lipase promoter via E-box dependent and independent mechanisms.
MedLine Citation:
PMID:  19416648     Owner:  NLM     Status:  MEDLINE    
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.
Diederik van Deursen; Marije van Leeuwen; Sophie Vaulont; Hans Jansen; Adrie J M Verhoeven
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-01-31
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1791     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-05-08     Completed Date:  2009-06-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  229-37     Citation Subset:  IM    
Department of Biochemistry, Cardiovascular Research School COEUR, Erasmus MC, NL-3000 CA Rotterdam, The Netherlands.
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MeSH Terms
COS Cells
Carcinoma, Hepatocellular / genetics,  metabolism,  pathology
Cercopithecus aethiops
Chromatin Immunoprecipitation
E-Box Elements / genetics*
Electrophoretic Mobility Shift Assay
Gene Expression Regulation, Enzymologic / physiology*
Gene Expression Regulation, Neoplastic
Lipase / genetics*,  metabolism
Liver Neoplasms / genetics,  metabolism,  pathology
Promoter Regions, Genetic / genetics*
RNA, Messenger / genetics,  metabolism
RNA, Small Interfering / pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Tumor Cells, Cultured
Upstream Stimulatory Factors / physiology*
Reg. No./Substance:
0/RNA, Messenger; 0/RNA, Small Interfering; 0/USF1 protein, human; 0/USF2 protein, human; 0/Upstream Stimulatory Factors; EC; EC lipase, human

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