First Author | Yokomori N | Year | 1997 |
Journal | J Steroid Biochem Mol Biol | Volume | 62 |
Issue | 4 | Pages | 307-14 |
PubMed ID | 9408084 | Mgi Jnum | J:44977 |
Mgi Id | MGI:1101555 | Doi | 10.1016/s0960-0760(97)00048-4 |
Citation | Yokomori N, et al. (1997) Transcriptional regulation by HNF-4 of the steroid 15alpha-hydroxylase P450 (Cyp2a-4) gene in mouse liver. J Steroid Biochem Mol Biol 62(4):307-14 |
abstractText | The mouse P450 gene Cyp2a-4 encodes the hepatic steroid 15apha-hydroxylase. We have defined in the 5'-flanking sequence of Cyp2a-4 gene, a composite regulatory element (-61AGACCAAAGTCCGGCCTTC-42) which contains a potential CpG methylation site at position -50. Gel-shift assays indicate that this element consists of overlapped binding sites for a hepatocyte-enriched transcription factor HNF-4 and a Sp1-like protein. Moreover, transcription of the Cyp2a-4 gene is activated by coexpression of HNF-4 in HepG2 cells. A mutation (C at -50 to A) abolishes the binding of HNF-4 to the element as well as the transcriptional activation by HNF-4. The methylated C at position -50, however, does not affect HNF-4 binding. Neither the mutation nor the methylation at position -50 affect the binding of Sp1-like protein to the element. It appears, therefore, that HNF-4 activates the hepatic transcription of Cyp2a-4 gene through its direct binding to the regulatory element regardless of the methylation at position -50. |