TY - JOUR
T1 - 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
AU - Buggs, Colleen
AU - Nasrin, Nargis
AU - Mode, Agneta
AU - Tollet, Petra
AU - Zhao, Hui Fen
AU - Gustafsson, Jan Åke
AU - Alexander-Bridges, Maria
PY - 1998
Y1 - 1998
N2 - 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.
AB - 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.
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U2 - 10.1210/mend.12.9.0174
DO - 10.1210/mend.12.9.0174
M3 - Article
C2 - 9731699
AN - SCOPUS:0032160175
SN - 0888-8809
VL - 12
SP - 1294
EP - 1309
JO - Molecular Endocrinology
JF - Molecular Endocrinology
IS - 9
ER -