An overview on experimental observations that demonstrate an involvement of C/EBPs in the transcriptional regulation of hepatic cytochrome P450 (CYP) genes
| CYP Gene | Cell Cultures | Experimental Approach | Agonistic TFs | Antagonistic TFs | C/EBP-Binding | Authors |
|---|---|---|---|---|---|---|
| Human CYP2B6 | Human HepG2 cells | Transfection with Zn-inducible C/EBP-α vector to achieve C/EBP-α reexpression | C/EBP-α | Jover et al., 1998 | ||
| Human CYP2C9 | Human HepG2 cells | Transfection with Zn-inducible C/EBP-α vector to achieve C/EBP-α reexpression | C/EBP-α | Jover et al., 1998 | ||
| Human CYP2D6 | Human HepG2 cells | Transfection with Zn-inducible C/EBP-α vector to achieve C/EBP-α reexpression | C/EBP-α | Jover et al., 1998 | ||
| Rat CYP2C12 (female specific) | Primary rat hepatocytes | C/EBP-α overexpression in the presence and absence of IRE-ABP, and DNase I footprint analysis, gel mobility shift assays | C/EBP-α | IRE-ABP | nts −222 to −204 | Buggs et al., 1998 |
| Human CYP3A4 | Human HepG2 cells | Cotransfection of C/EBP-α and DBP plus promotor deletion experiments with reporter gene assay | C/EBP-α | nts −57 to +11 | Ourlin et al., 1997 | |
| Human CYP3A7 | Human HepG2 cells | Cotransfection of C/EBP-α and DBP plus promotor deletion experiments with reporter gene assay | C/EBP-α | nts −55 to +13 | Ourlin et al., 1997 | |
| Chicken CYP2H1 | Chicken embryo hepatocytes, human HepG2 cells, COS-1 cells | Promotor deletion experiments and DNase I footprint analysis, gel mobility shift assays | Rat HNF-1α, rat HNF-1β, rat HNF-3α or -β and chicken C/EBP-α | USF (repression, derepression by phenobarbital through competition at Barbie-box-like sequence) | Dogra and May, 1997 | |
| Rat CYP2B1 | Human HepG2 cells | Promotor deletion experiments and DNase I footprint analysis, gel mobility shift assays | C/EBP-α | nts −64 to −45 | Park and Kemper, 1996 | |
| Rat CYP2B1 | Nuclear extracts from rat livers, primary rat hepatocytes | Promotor deletion experiments and DNase I footpring analysis, gel mobility shift assays, in vitro transfection assay | C/EBP-α | nts −66 to −42 | Luc et al., 1996 | |
| Rat CYP2B2 | Primary rat hepatocytes | Promotor deletion experiments and DNase I footprint analysis, gel mobility shift assays, in vitro transfection assay | C/EBP-α | nts −66 to −42 | Luc et al., 1996 | |
| Rat CYP2C12 | Primary rat hepatocytes | Transient transfection of a C/EBP-α expression vector plus promotor deletion experiments with reporter gene assay, DNase I footprint analysis, gel mobility supershift assays | C/EBP-α | nts −229 to −207 | Tollet et al., 1995 | |
| Rat CYP2D5 | Human HepG2 cells, Drosophila melanogaster cells | Transient transfection of a C/EBP-α or C/EBP-β or HNF-1 or a DBP expression vector plus promotor deletion experiments with reporter gene assay, DNase I footprint analysis, gel mobility supershift assays | Sp1, C/EBP-β forms a ternary complex with a possible agonistic protein-protein interaction Sp1-C/EBP-β | Lee et al., 1994a |
IRE-ABP, insulin response element-A binding protein; TF, transcriptional factor; nts = nucleotides numbered in relation to the start site of transcription within the respective promoter of the CYP gene; agonistic TFs = transcription factors that enhance CYP gene expression; antagonistic TFs = transcription factors that inhibit CYP gene expression.