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URL Address
<a href="http://doi.org/10.1006/abbi.2000.1836" target="_blank" rel="noreferrer noopener">http://doi.org/10.1006/abbi.2000.1836</a>
Pages
364–376
Issue
2
Volume
378
Dublin Core
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Title
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Promoter activity and regulation of the CYP4F2 leukotriene B(4) omega-hydroxylase gene by peroxisomal proliferators and retinoic acid in HepG2 cells.
Publisher
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Archives of biochemistry and biophysics
Date
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2000
2000-06
Subject
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*Gene Expression Regulation; *Promoter Regions; Amino Acid Sequence; Base Sequence; Cell Line; Cloning; Cytochrome P-450 CYP4A; Cytochrome P-450 Enzyme System/*genetics/metabolism; Cytochrome P450 Family 4; Cytoplasmic and Nuclear/metabolism; DNA; DNA Footprinting; Enzymologic; Exons; Genes; Genetic; Genetic/drug effects; Humans; Introns; Leukotriene B4/metabolism; Mixed Function Oxygenases/metabolism; Models; Molecular; Molecular Sequence Data; Peroxisome Proliferators/*metabolism; Receptors; Reporter; Retinoic Acid Receptor alpha; Retinoic Acid/metabolism; Sequence Analysis; Transcription; Transcription Factors/metabolism; Transfection; Tretinoin/*metabolism
Creator
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Zhang X; Chen L; Hardwick J P
Description
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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
Identifier
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<a href="http://doi.org/10.1006/abbi.2000.1836" target="_blank" rel="noreferrer noopener">10.1006/abbi.2000.1836</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Gene Expression Regulation
*Promoter Regions
2000
Amino Acid Sequence
Archives of biochemistry and biophysics
Base Sequence
Cell Line
Chen L
Cloning
Cytochrome P-450 CYP4A
Cytochrome P-450 Enzyme System/*genetics/metabolism
Cytochrome P450 Family 4
Cytoplasmic and Nuclear/metabolism
Department of Integrative Medical Sciences
DNA
DNA Footprinting
Enzymologic
Exons
Genes
Genetic
Genetic/drug effects
Hardwick J P
Humans
Introns
Leukotriene B4/metabolism
Mixed Function Oxygenases/metabolism
Models
Molecular
Molecular Sequence Data
NEOMED College of Medicine
Peroxisome Proliferators/*metabolism
Receptors
Reporter
Retinoic Acid Receptor alpha
Retinoic Acid/metabolism
Sequence Analysis
Transcription
Transcription Factors/metabolism
Transfection
Tretinoin/*metabolism
Zhang X