Transactivation of the rat CYP2C13 gene promoter involves HNF-1, HNF-3, and members of the orphan receptor subfamily.
The rat CYP2C13 gene (2C13) encodes one of the constitutive male forms of cytochrome P-450 that are involved in steroid metabolism. In addition to being developmentally regulated, the expression of 2C13 is restricted to the liver and suppressed by the female pattern of growth hormone (GH) secretion at the transcriptional initiation level. In this study, we show that the liver-specific expression, but not the regulation by GH, can be reconstituted with 117 bp to 2 kb of 2C13 5' flank. Transactivation of the 2C13 promoter requires both HNF-1 and HNF-3 and is influenced by members of the orphan receptor subfamily of transcription factors. Although HNF-4, ARP-1, EAR-2, and COUP-TF bind to the 2C13 promoter in vitro, overexpression of EAR-2 and COUP-TF, but not of HNF-4 or ARP-1, results in the potentiation of the HNF-3- and HNF-1-supported activity in non-liver cells.
Legraverend
C
C
Department of Medical Nutrition, Karolinska Institute, Huddinge, Sweden.
Eguchi
H
H
Ström
A
A
Lahuna
O
O
Mode
A
A
Tollet
P
P
Westin
S
S
Gustafsson
J A
JA
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D051541:Hepatocyte Nuclear Factor 3-alpha; D051542:Hepatocyte Nuclear Factor 3-beta; D051543:Hepatocyte Nuclear Factor 3-gamma; D051557:Hepatocyte Nuclear Factor 4; D007016:Hypophysectomy; D008099:Liver / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000378:metabolism / Q000494:pharmacology*; D010750:Phosphoproteins; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D012045:Regulatory Sequences, Nucleic Acid; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000378:metabolism / Q000494:pharmacology; D015533:Transcriptional Activation; D014162:Transfection
D004268:DNA-Binding Proteins; C496501:Foxa1 protein, rat; C496504:Foxa2 protein, rat; C496507:Foxa3 protein, rat; D051538:Hepatocyte Nuclear Factor 1-alpha; D051541:Hepatocyte Nuclear Factor 3-alpha; D051557:Hepatocyte Nuclear Factor 4; C496489:Hnf1a protein, rat; D009687:Nuclear Proteins; D010750:Phosphoproteins; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051543:Hepatocyte Nuclear Factor 3-gamma; D051542:Hepatocyte Nuclear Factor 3-beta; D051539:Hepatocyte Nuclear Factor 1-beta; D004247:DNA; D003577:Cytochrome P-450 Enzyme System