Drug Metabolism and Pharmacokinetics
Print ISSN : 0916-1139
Structural organization and characterization of the regulatory element of human carboxylesterase gene
Masakiyo HOSOKAWAEiko TSUKADANatsuko WATANABEYoshiko OHHATAMaki FUKUMOTOYuko OGASAWARAHironobu MINAMIHirofumi FUJIIYasutsuna SASAKISeishi NAGAMORIKan CHIBA
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2000 Volume 15 Issue supplement Pages 78-79

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Abstract

A gene encoding a 5' flanking region of human carboxylesterase(CES) has been cloned and characterized. Analysis of genomic lambda clone H2B revealed that the gene spans about 1, 021 bp. This clone include an in-frame initiation codon (ATG) of human liver CES isozyme HU1, and the clone completely overlap the CES HU1 cDNA. The transcription start site was determined by CAP-Site hanting methods. An additional 892 by of DNA from the 5' flanking region of the gene was cloned and sequenced in order to elucidate the structure of the promoter. In this sequence several possible binding sites for transcription factors have been identified, but TATA-box was not present. The putative promoter region was investigated by gel mobility shift assay and the reporter gene assay. The promoter region include HNF-1, CCAAT-Box, GC-box and initiator. We also observed genetic polymorphism of a 5' flanking region of human liver CES by PCR-SSCP analysis and DNA sequence of individual human livers. These results suggest that the individual differences of human liver esterase activity may be, at least in part, dependent on the genetic polymorphism of a 5' flanking region of CES HU1.

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© The Japanese Society for the Study of Xenobiotics
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