Evidence map›Paper›PMID 17428321›Full record

ArticleBMC genomics2007

Comparative genomics and experimental promoter analysis reveal functional liver-specific elements in mammalian hepatic lipase genes.

Diederik van Deursen, Gert-Jan Botma, Hans Jansen, Adrie J M Verhoeven

Open access · goldAbstract readComparative Study
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
2.3field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 13 citations in OpenAlex.

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4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Diederik van DeursenDepartment of Biochemistry, Cardiovascular Research School COEUR, Erasmus MC, Rotterdam, The Netherlands. d.vandeursen@erasmusmc.nl
Gert-Jan Botma
Hans Jansen
Adrie J M Verhoeven
Erasmus University Rotterdam · NLErasmus MC · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Promoter Regions, GeneticAnimalsGenes, ReporterGenomicsHeLa CellsHumansLipaseLiverMacaca mulattaMammalsMiceOrgan SpecificityRatsSequence Analysis, DNATranscription, GeneticTumor Cells, CulturedLipaseLIPC protein, human

Identifiers

PMID17428321
PMCPMC1853088
OpenAlexW1976688235

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.