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http://hdl.handle.net/2445/48746
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DC Field | Value | Language |
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dc.contributor.author | Prieur, Xavier | - |
dc.contributor.author | Schaap, Frank G. | - |
dc.contributor.author | Coste, Hervé | - |
dc.contributor.author | Rodríguez Rubio, Joan Carles | - |
dc.date.accessioned | 2014-01-09T09:13:07Z | - |
dc.date.available | 2014-01-09T09:13:07Z | - |
dc.date.issued | 2005-12-01 | - |
dc.identifier.issn | 0888-8809 | - |
dc.identifier.uri | http://hdl.handle.net/2445/48746 | - |
dc.description.abstract | The recently discovered apolipoprotein AV (apoAV) gene has been reported to be a key player in modulating plasma triglyceride levels. Here we identify the hepatocyte nuclear factor-4 (HNF-4 ) as a novel regulator of human apoAV gene. Inhibition of HNF-4 expression by small interfering RNA resulted in down-regulation of apoAV. Deletion, mutagenesis, and binding assays revealed that HNF-4 directly regulates human apoAV promoter through DR1 [a direct repeat separated by one nucleotide (nt)], and via a novel element for HNF-4 consisting of an inverted repeat separated by 8 nt (IR8). In addition, we show that the coactivator peroxisome proliferator-activated receptor- coactivator-1 was capable of stimulating the HNF-4 -dependent transactivation of apoAV promoter. Furthermore, analyses in human hepatic cells demonstrated that AMP-activated protein kinase (AMPK) and the MAPK signaling pathway regulate human apoAV expression and suggested that this regulation may be mediated, at least in part, by changes in HNF-4 . Intriguingly, EMSAs and mice with a liver-specific disruption of the HNF-4 gene revealed a species-distinct regulation of apoAV by HNF-4 , which resembles that of a subset of HNF-4 target genes. Taken together, our data provide new insights into the binding properties and the modulation of HNF-4 and underscore the role of HNF-4 in regulating triglyceride metabolism. | - |
dc.format.extent | 19 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Endocrine Society | - |
dc.relation.isformatof | Reproducció del document publicat a: http://dx.doi.org/10.1210/me.2005-0048 | - |
dc.relation.ispartof | Molecular Endocrinology, 2005, vol. 19, num. 12, p. 3107-3125 | - |
dc.relation.uri | http://dx.doi.org/10.1210/me.2005-0048 | - |
dc.rights | (c) Endocrine Society, 2005 | - |
dc.source | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) | - |
dc.subject.classification | Lipoproteïnes | - |
dc.subject.classification | Genètica | - |
dc.subject.classification | Receptors nuclears (Bioquímica) | - |
dc.subject.classification | Factors de transcripció | - |
dc.subject.classification | Àcids nucleics | - |
dc.subject.other | Lipoproteins | - |
dc.subject.other | Genetics | - |
dc.subject.other | Nuclear receptors (Biochemistry) | - |
dc.subject.other | Transcription factors | - |
dc.subject.other | Nucleic acids | - |
dc.title | Hepatocyte nuclear factor-4 alpha regulates the human apolipoprotein AV gene: Identification of a novel response element and involvement in the control by peroxisome proliferator-activated receptor-gamma coactivator-1 alpha, AMP-activated protein kinase, and mitogen-activated protein kinase pathway | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 570940 | - |
dc.date.updated | 2014-01-09T09:13:07Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) |
Files in This Item:
File | Description | Size | Format | |
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570940.pdf | 621.11 kB | Adobe PDF | View/Open |
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