The pig CYP2E1 promoter is activated by COUP-TF1 and HNF-1 and is inhibited by androstenone

Tambyrajah , W. S., Doran (nee Udovikova), O., Wood, J. D. and McGivan, J. D. (2004) The pig CYP2E1 promoter is activated by COUP-TF1 and HNF-1 and is inhibited by androstenone. Archives of Biochemistry and Biophsics, 431 (2). pp. 252-260. ISSN 0003-9861

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Publisher's URL: http://dx.doi.org/10.1016/j.abb.2004.08.016

Abstract

Functional analysis of the pig cytochrome P4502E1 (CYP2E1) promoter identified two major activating elements. One corresponded to the hepatic nuclear factor 1 (HNF-1) consensus binding sequence at nucleotides −128/−98 and the other was located in the region −292/−266. The binding of proteins in pig liver nuclear extracts to a synthetic double-stranded oligonucleotide corresponding to this more distal activating sequence was studied by electrophoretic mobility shift assay. The minimum protein binding sequence was identified as TGTTCTGACCTCTGGG. Gel super-shift assays identified the protein binding to this site as chick ovalbumin upstream promoter transcription factor 1 (COUP-TF1). Androstenone inhibited promoter activity in transfection experiments only with constructs which included the COUP-TF1 binding site. Androstenone inhibited COUP-TF1 binding to synthetic oligonucleotides but did not affect HNF-1 binding. The results offer an explanation for the inhibition of CYP2E1 protein expression by androstenone in isolated pig hepatocytes and may be relevant to the low expression of hepatic CYP2E1 in those pigs which accumulate high levels of androstenone in vivo.

Item Type:Article
Uncontrolled Keywords:porcine CYP2E1 promoter, transcription factors COUPTF1 and HNF1, androstenone
Faculty/Department:Faculty of Health and Applied Sciences > Department of Biological, Biomedical and Analytical Sciences
ID Code:14906
Deposited By: Professor O. Doran
Deposited On:10 Jun 2011 11:10
Last Modified:12 Aug 2013 08:05

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