Source:http://linkedlifedata.com/resource/pubmed/id/10860554
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2000-7-17
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| pubmed:abstractText |
The human liver CYP4F2 gene (Accession No. AF221943) encodes a leukotriene B(4) omega-hydroxylase that metabolizes leukotriene B(4) (LTB(4)) to a less potent proinflammatory eicosanoid, 20-OH-LTB(4). We sequenced a 6.7-kb genomic fragment of the human CYP4F2 gene that has the first five exons and 500 bp of the 5'-flanking region. The major transcription start site was found to be 49 bp upstream of the 3' end of exon 1 and the ATG translation initiation codon was located in exon 2. Besides the TATA box at -39 bp and basal transcription factor binding sites, the promoter region and 412-bp intron 1 have several putative binding sites for nuclear factors that may mediate the inflammatory response and lipid homeostasis. We found two DR1 elements in the 5' promoter, a DR2 element in intron 1, and RXR/RAR binding sites in both intron 1 and the 5' promoter. DNase I footprinting revealed three protected sequences, with the region containing two CAATT boxes at -71 and -111 bp important in CYP4F2 gene expression. Luciferase reporter assays showed that the 500-bp upstream sequence has strong promoter activity. Transient transfection experiments identified two sites in the 5' promoter and intron 1 that cooperate in gene transcription while exon 1 and a GC-rich region flanking exon 1 inhibit transcription. trans-Retinoic acid and 9-cis-retinoic acid stimulate promoter activity 3- and 6-fold, respectively, while cotransfection with RXRalpha or RAR/RXRalpha further enhanced activity. Peroxisome proliferators inhibit CYP4F2 gene promoter activity and cotransfection with PPARalpha or PPARalpha/RXRalpha can slightly attenuate this inhibition. Both saturated fatty acids and 12-hydroxydodecanoic acid (12-OH-C(12)) can stimulate CYP4F2 gene promoter activity. Therefore, the CYP4F2 gene is repressed by peroxisomal proliferators and induced by retinoic acid, with RAR/RXRalpha mediating the induction while PPARalpha/RXR functions neither in the repression nor in the induction by peroxisomal proliferators or retinoic acid.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Alkane 1-Monooxygenase,
http://linkedlifedata.com/resource/pubmed/chemical/CYP4F2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System,
http://linkedlifedata.com/resource/pubmed/chemical/Leukotriene B4,
http://linkedlifedata.com/resource/pubmed/chemical/Mixed Function Oxygenases,
http://linkedlifedata.com/resource/pubmed/chemical/Peroxisome Proliferators,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Retinoic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tretinoin,
http://linkedlifedata.com/resource/pubmed/chemical/retinoic acid receptor alpha
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jun
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| pubmed:issn |
0003-9861
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| pubmed:author | |
| pubmed:copyrightInfo |
Copyright 2000 Academic Press.
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| pubmed:issnType |
Print
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| pubmed:day |
15
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| pubmed:volume |
378
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
364-76
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:10860554-Alkane 1-Monooxygenase,
pubmed-meshheading:10860554-Amino Acid Sequence,
pubmed-meshheading:10860554-Base Sequence,
pubmed-meshheading:10860554-Cell Line,
pubmed-meshheading:10860554-Cloning, Molecular,
pubmed-meshheading:10860554-Cytochrome P-450 Enzyme System,
pubmed-meshheading:10860554-DNA Footprinting,
pubmed-meshheading:10860554-Exons,
pubmed-meshheading:10860554-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:10860554-Genes, Reporter,
pubmed-meshheading:10860554-Humans,
pubmed-meshheading:10860554-Introns,
pubmed-meshheading:10860554-Leukotriene B4,
pubmed-meshheading:10860554-Mixed Function Oxygenases,
pubmed-meshheading:10860554-Models, Genetic,
pubmed-meshheading:10860554-Molecular Sequence Data,
pubmed-meshheading:10860554-Peroxisome Proliferators,
pubmed-meshheading:10860554-Promoter Regions, Genetic,
pubmed-meshheading:10860554-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:10860554-Receptors, Retinoic Acid,
pubmed-meshheading:10860554-Sequence Analysis, DNA,
pubmed-meshheading:10860554-Transcription, Genetic,
pubmed-meshheading:10860554-Transcription Factors,
pubmed-meshheading:10860554-Transfection,
pubmed-meshheading:10860554-Tretinoin
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| pubmed:year |
2000
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| pubmed:articleTitle |
Promoter activity and regulation of the CYP4F2 leukotriene B(4) omega-hydroxylase gene by peroxisomal proliferators and retinoic acid in HepG2 cells.
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| pubmed:affiliation |
Department of Biochemistry and Molecular Pathology, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio 44272, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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