ArticleBMC genomics2007
Comparative genomics and experimental promoter analysis reveal functional liver-specific elements in mammalian hepatic lipase genes.
Article in BMC genomics, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed, 13 citations in OpenAlex.
- HCV IRES-mediated core expression in zebrafish.PloS one · 2013Article
- In silico promoters: modelling of cis-regulatory context facilitates target predictio.Journal of cellular and molecular medicine · 2009Review
- Positional bias of general and tissue-specific regulatory motifs in mouse gene promoters.BMC genomics · 2007Article
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4 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundMammalian hepatic lipase (HL) genes are transcribed almost exclusively in hepatocytes. The basis for this liver-restricted expression is not completely understood. We hypothesized that the responsible cis-acting elements are conserved among mammalian HL genes. To identify these elements, we made a genomic comparison of 30 kb of 5'-flanking region of the rat, mouse, rhesus monkey, and human HL genes. The in silico data were verified by promoter-reporter assays in transfected hepatoma HepG2 and non-hepatoma HeLa cells using serial 5'-deletions of the rat HL (-2287/+9) and human HL (-685/+13) promoter region.
resultsHighly conserved elements were present at the proximal promoter region, and at 14 and 22 kb upstream of the transcriptional start site. Both of these upstream elements increased transcriptional activity of the human HL (-685/+13) promoter region 2-3 fold. Within the proximal HL promoter region, conserved clusters of transcription factor binding sites (TFBS) were identified at -240/-200 (module A), -80/-40 (module B), and -25/+5 (module C) by the rVista software. In HepG2 cells, modules B and C, but not module A, were important for basal transcription. Module B contains putative binding sites for hepatocyte nuclear factors HNF1alpha. In the presence of module B, transcription from the minimal HL promoter was increased 1.5-2 fold in HepG2 cells, but inhibited 2-4 fold in HeLa cells.
conclusionOur data demonstrate that searching for conserved non-coding sequences by comparative genomics is a valuable tool in identifying candidate enhancer elements. With this approach, we found two putative enhancer elements in the far upstream region of the HL gene. In addition, we obtained evidence that the -80/-40 region of the HL gene is responsible for enhanced HL promoter activity in hepatoma cells, and for silencing HL promoter activity in non-liver cells.
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