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rdf:type |
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lifeskim:mentions |
umls-concept:C0017337,
umls-concept:C0020792,
umls-concept:C0205314,
umls-concept:C0227525,
umls-concept:C0521447,
umls-concept:C0600508,
umls-concept:C0679622,
umls-concept:C0752312,
umls-concept:C0851285,
umls-concept:C1310227,
umls-concept:C1314939,
umls-concept:C1335238,
umls-concept:C1704259,
umls-concept:C1705987,
umls-concept:C2350345,
umls-concept:C2587213
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pubmed:issue |
12
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pubmed:dateCreated |
2005-11-24
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pubmed:abstractText |
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-4alpha (HNF-4alpha) as a novel regulator of human apoAV gene. Inhibition of HNF-4alpha expression by small interfering RNA resulted in down-regulation of apoAV. Deletion, mutagenesis, and binding assays revealed that HNF-4alpha directly regulates human apoAV promoter through DR1 [a direct repeat separated by one nucleotide (nt)], and via a novel element for HNF-4alpha consisting of an inverted repeat separated by 8 nt (IR8). In addition, we show that the coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha was capable of stimulating the HNF-4alpha-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-4alpha. Intriguingly, EMSAs and mice with a liver-specific disruption of the HNF-4alpha gene revealed a species-distinct regulation of apoAV by HNF-4alpha, which resembles that of a subset of HNF-4alpha target genes. Taken together, our data provide new insights into the binding properties and the modulation of HNF-4alpha and underscore the role of HNF-4alpha in regulating triglyceride metabolism.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/AMP-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/APOA5 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Apolipoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Apolipoproteins A,
http://linkedlifedata.com/resource/pubmed/chemical/Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Hepatocyte Nuclear Factor 4,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/PPARGC1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0888-8809
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
19
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3107-25
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16051671-AMP-Activated Protein Kinases,
pubmed-meshheading:16051671-Animals,
pubmed-meshheading:16051671-Apolipoproteins,
pubmed-meshheading:16051671-Apolipoproteins A,
pubmed-meshheading:16051671-Cells, Cultured,
pubmed-meshheading:16051671-Gene Deletion,
pubmed-meshheading:16051671-Gene Expression Regulation,
pubmed-meshheading:16051671-Heat-Shock Proteins,
pubmed-meshheading:16051671-Hepatocyte Nuclear Factor 4,
pubmed-meshheading:16051671-Hepatocytes,
pubmed-meshheading:16051671-Humans,
pubmed-meshheading:16051671-Mice,
pubmed-meshheading:16051671-Mice, Mutant Strains,
pubmed-meshheading:16051671-Mitogen-Activated Protein Kinases,
pubmed-meshheading:16051671-Multienzyme Complexes,
pubmed-meshheading:16051671-Promoter Regions, Genetic,
pubmed-meshheading:16051671-Protein-Serine-Threonine Kinases,
pubmed-meshheading:16051671-RNA, Small Interfering,
pubmed-meshheading:16051671-Repetitive Sequences, Nucleic Acid,
pubmed-meshheading:16051671-Response Elements,
pubmed-meshheading:16051671-Transcription Factors
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pubmed:year |
2005
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pubmed:articleTitle |
Hepatocyte nuclear factor-4alpha regulates the human apolipoprotein AV gene: identification of a novel response element and involvement in the control by peroxisome proliferator-activated receptor-gamma coactivator-1alpha, AMP-activated protein kinase, and mitogen-activated protein kinase pathway.
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pubmed:affiliation |
GlaxoSmithKline, 25 avenue du Québec, 91951 Les Ulis cedex, France.
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pubmed:publicationType |
Journal Article
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