Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.649560
Title: Characterisation of the human CYP2A7 gene : an analysis of its structure, regulation and expression
Author: Ding, Shaohong
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1995
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Abstract:
A human gene, encoding a protein highly homologous to CYP2A7, has been isolated. Only thirteen base pair differences resulting in five amino acid changes were found. Genomic analysis demonstrated that the isolated gene is an allele of CYP2A7, designated CYP2A7A. The gene is about 8 kb long and contains 9 exons encoding a protein of 494 amino acids. The 0.5 kb 5' flanking region of CYP2A7A contained several putative promoter elements including a typical TATA box, a steroid regulatory element (SRE), and a HepG2-specific factor-1 binding sequence (HPF-1). The presence of HPF-1 motif was essential for the transcription of the gene in HepG2 cells. However, the function of SRE element is still unclear. In order to investigate the relationship between the expression levels of human CYP2A genes and the polymorphisms of coumarin hydroxylase activity in man, three cDNAs, CYP2A6, CYP2A7 and an alternatively spliced version of CYP2A7 (CYP2A7AS) have been cloned. The later one was missing exon 2 but contained a 10 bp segment of intron 1. Translation of the CYP2A7AS resulted in an in frame deletion of 51 amino acids. The expression of these cDNA's in COS-7 cells showed that both CYP2A6 and CYP2A7 generated a protein Mr 49 kDa, while the protein product of CYP2A7AS was about 44 kDa. Only the CYP2A6 had coumarin hydroxylase activity. The relative level of mRNA encoding CYP2A6 and CYP2A7 was established in six human liver samples with RT-PCR followed by PstI digestion and found to range between 1:0.5 to 1:3, respectively. These results showed that the relative level of CYP2A7 was variable.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.649560  DOI: Not available
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