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Publication : Transcriptional regulation by HNF-4 of the steroid 15alpha-hydroxylase P450 (Cyp2a-4) gene in mouse liver.

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.
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