Transcription of the human hepatic lipase gene is modulated by multiple negative elements in HepG2 cells

Gene
K OkaL Chan

Abstract

The expression of the hepatic lipase (HL) gene is highly tissue specific. In order to identify cis-acting elements which regulate the expression of this gene in the liver, multiple deletion mutants of the 5'-flanking region of the HL gene fused to the human growth hormone gene were transfected in HepG2 cells, which normally produce HL. Transient expression assays indicated the presence of negative (at nucleotides (nt) -1576(/)-1342 and -623(/)-407) and positive (at nt -1862(/)-1576 and -50(/)-9) regulatory elements. Transfection of HeLa cells, which do not produce HL, with the same deletion constructs resulted in a similar pattern of promoter activities. However, additional negative (nt -138/-50) and positive (nt -407(/)-138) elements were found. DNase I footprint analysis of the proximal and distal HLpromoter sequences with HepG2 and HeLa cell nuclear extracts identified seven protected regions: A, nt -1540(/)-1527; B, -1505(/)-1473; C, -1467(/)-1460; D, -592(/)-577; E, -565(/)-545; F, -234(/)-220; and G, -70(/) -48. Sites A, B, C, D and E were located within regions containing negative regulatory elements. In order to determine which nuclear factor interacts with the negative elements, sites B, D and E were mutated and the ef...Continue Reading

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Citations

Jul 1, 1997·European Journal of Biochemistry·S F ChangH Will
Apr 11, 2006·Journal of Lipid Research·Laura E RufibachSamir S Deeb
May 16, 2000·Arteriosclerosis, Thrombosis, and Vascular Biology·F M van't HooftA Hamsten

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