Hepatocyte Nuclear Factor 4α Regulates Expression of the Mouse Female-SpecificCyp3a41Gene in the Liver
| Autor: | Yuki Kawasaki, Nobuo Nemoto, Wattanaporn Bhadhprasit, Tsutomu Sakuma |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Aging Pharmaceutical Science Biology Methylation Gene Expression Regulation Enzymologic Histones Mice Cytochrome P-450 Enzyme System medicine Animals RNA Messenger Promoter Regions Genetic Gene Transcription factor Cells Cultured Hypophysectomy Cell Nucleus Pharmacology Sex Characteristics Reporter gene Expression vector Human Growth Hormone Acetylation Molecular biology Chromatin Recombinant Proteins DNA-Binding Proteins Hepatocyte nuclear factors medicine.anatomical_structure Hepatocyte Nuclear Factor 4 Liver Hepatocyte Female Chromatin immunoprecipitation |
| Zdroj: | Drug Metabolism and Disposition. 39:490-497 |
| ISSN: | 1521-009X 0090-9556 |
| DOI: | 10.1124/dmd.110.035980 |
| Popis: | CYP3A41 is a female-specific cytochrome P450 in mouse liver. A putative hepatocyte nuclear factor 4α (HNF4α)-binding site was found at -99/-87 in the promoter of Cyp3a41 by reporter assays performed in the hepatocytes of female mice. Cotransfection of an HNF4α expression plasmid significantly increased transcription of the reporter gene. Although electrophoretic mobility shift assays with liver nuclear extracts did not show a sex-related difference, chromatin immunoprecipitation (ChIP) assays showed that larger amounts of HNF4α bound to Cyp3a41 in female than in male mice. A relation between the amount of HNF4α on the Cyp3a41 gene and mRNA expression was observed in hepatic tissue sets, which differ in mRNA expression depending on the sex, age, or endocrine status of mice. The degree of histone-3-lysine-4 dimethylation and histone-3-lysine-27 trimethylation around the HNF4α-binding site was higher in females and males, respectively. Moreover, the ChIP assay indicated greater acetylation of histone-4-lysine-8 of the Cyp3a41 chromatin in females than in males. HNF4α plays an important role in the transcriptional activation of the Cyp3a41 gene, and a sex difference in chromatin structure may contribute to the female-specific expression of Cyp3a41 in the livers of mice. |
| Databáze: | OpenAIRE |
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