CYP2B1 is regulated by C/EBP alpha and C/EBP delta inlung epithelial cells.
Pulmonary expression of several cytochrome P450 (CYP) monooxygenases is detected late in gestation. Little is known of the factors involved in this differentiation-dependent expression. C/EBP factors are known regulators of differentiation and differentiation-dependent gene expression in several tissues. In this study we demonstrate the importance of C/EBP alpha and C/EBP delta in pulmonary epithelial CYP2B1 gene expression. A 1.3 kb CYP2B1 promoter fragment which recently has been shown to confer lung tissue- and cell-specific expression of CYP2B1 in transgenic mice was used in transient transfection studies. Both C/EBP alpha and C/EBP delta transactivated the CYP2B1 promoter in the lung epithelial cell lines A549 and NCI-H441. C/EBP alpha in nuclear extracts from isolated rat primary bronchiolar Clara cells was capable of interacting with a C/EBP-binding site in the proximal CYP2B1 promoter. Site-directed mutagenesis studies showed that this proximal C/EBP-binding site is necessary for transactivation of the CYP2B1 gene by C/EBP alpha and C/EBP delta. Thi study shows that C/EBP factors have a role in pulmonary CYP2B1 expression and suggests that these transcription factors may be important for the differentiation-dependent expression of CYP2B1 in the lung.
Cassel
T N
TN
Department of Medical Nutrition, Karolinska Institutet, Huddinge University Hospital, F60 Novum, Huddinge, S-141 86, Sweden.
Gustafsson
J A
JA
Nord
M
M
D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D001980:Bronchi / Q000166:cytology / Q000201:enzymology; D051743:CCAAT-Enhancer-Binding Protein-delta; D022762:CCAAT-Enhancer-Binding Proteins; D019556:COS Cells; D002460:Cell Line; D002478:Cells, Cultured; D019362:Cytochrome P-450 CYP2B1 / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004847:Epithelial Cells / Q000201:enzymology*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008168:Lung / Q000201:enzymology*; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D014157:Transcription Factors; D015533:Transcriptional Activation; D014162:Transfection
D022762:CCAAT-Enhancer-Binding Proteins; C497252:CEBPD protein, human; C497254:Cebpd protein, rat; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D051743:CCAAT-Enhancer-Binding Protein-delta; D019362:Cytochrome P-450 CYP2B1