Hepatocyte Nuclear Factor 4-Mediated Activation of Rat CYP3A1 Gene and Its Modes of Modulation by Apolipoprotein AI Regulatory Protein I and v-ErbA-Related Protein 3

doi:10.1006/abbi.1998.1012

Archives of Biochemistry and Biophysics

Volume 362, Issue 1, 1 February 1999, Pages 32-37

https://doi.org/10.1006/abbi.1998.1012 Get rights and content

Abstract

CYP3A1 gene (P450/6βB) encodes testosterone 6β-hydroxylase (EC 1.14.14.1) in rats. The promoter region of CYP3A1 gene contains three binding sites for nuclear factors: 6βB-A (−105 to −86), 6βB-B (−139 to −118), and 6βB-C (−164 to −145). The 6βB-A site shows a high degree of similarity to a consensus sequence of the binding site of hepatocyte nuclear factor 4 (HNF-4) and also to the 6βA-A site on the rat CYP3A2 gene promoter region. Our previous study suggested an involvement of the 6βA-A site in the basal transactivation of CYP3A2 gene using HepG2 cells. In the present study, transactivation through the 6βB-A and 6βA-A sites of CYP3A1 and CYP3A2 genes has directly been shown by coexpression of HNF-4 and CYP3A1 or CYP3A2 promoter–reporter fused genes. Similar experiments further showed that nuclear factor binding at the 6βB-B site hampered HNF-4-mediated transactivation of CYP3A1 gene. Recombinant apolipoprotein AI regulatory protein I (ARP-1) and v-ErbA-related protein 3 (EAR-3) are shown to suppress HNF-4-mediated activation at the 6βB-B site without competition of HNF-4.

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Regular ArticleHepatocyte Nuclear Factor 4-Mediated Activation of Rat CYP3A1 Gene and Its Modes of Modulation by Apolipoprotein AI Regulatory Protein I and v-ErbA-Related Protein 3

Abstract

Arch. Biochem. Biophys.

Arch. Biochem. Biophys.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

Biochim. Biophys. Acta

Arch. Biochem. Biophys.

Biochim. Biophys. Acta

Cell

Cell

Pharmacogenetics

Pharmacol. Rev.

Regular Article
Hepatocyte Nuclear Factor 4-Mediated Activation of Rat CYP3A1 Gene and Its Modes of Modulation by Apolipoprotein AI Regulatory Protein I and v-ErbA-Related Protein 3