IRE-ABP (Insulin Response Element-A Binding Protein), an SRY-Like Protein, Inhibits C/EBPα (CCAAT/Enhancer-Binding Protein α)-Stimulated Expression of the Sex-Specific Cytochrome P450 2C12 Gene

Colleen Buggs, Nargis Nasrin, Agneta Mode, Petra Tollet, Hui Fen Zhao, Jan Åke Gustafsson, Maria Alexander-Bridges

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

In primary hepatocytes, overexpression of an insulin response element-A binding protein (IRE-ABP), a member of the SRY family of high-mobility group (HMG) proteins, inhibits CCAAT/enhancer-binding protein α (C/EBPα)-mediated activation of the female-specific cytochrome P450 2C12 (CYP2C12) gene, but not the male-specific cytochrome P450 2C11 (CYP2C11) gene. IRE-ABP and C/EBPa have overlapping specificity for the C/EBPα target site in the CYP2C12 promoter and compete for binding to CYP2C12 DNA in vitro. In contrast, IRE-ABP and C/EBPa bind distinct sequences in the CYP2C11 promoter. A single amino acid substitution in the HMG domain of IRE-ABP impairs its ability to bind DNA and to inhibit the effect of C/EBPα on CYP2C12 gene expression. Therefore, the ability of IRE-ABP to inhibit C/EBPα-stimulated CYP2C12 gene expression requires a functional DNA-binding domain. Taken together, our findings suggest that SRY-like proteins can bind to a subset of sequences recognized by the C/EBP family of DNA-binding proteins and modulate gene transcription in a context-specific manner.

Original languageEnglish (US)
Pages (from-to)1294-1309
Number of pages16
JournalMolecular Endocrinology
Volume12
Issue number9
DOIs
StatePublished - 1998

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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