| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Outline of Final Research Achievements |
Some of CYP3A genes including human CYP3A4 and mouse Cyp3a41 express female-predominantly. The objective of this study is to clarify the mechanisms, especially epi-genetic manner, for female-predominant expression. Our study demonstrated that female-dominant binding of HNF4a to the promoter (-99/-87) was involved in female specific expression of mouse Cyp3a41 gene. CHART-PCR analysis demonstrated that the chromatin prepared from female mouse hepatocytes was more relaxed than that from male hepatocytes. It is, therefore, likely that this difference is a cause of the female-dominant binding of HNF4a on Cyp3a41 gene. Reporter gene assay demonstrated that COUP-TFII and HNF4a interact in a synergic manner on Cyp3a41 gene in female hepatocytes. Thus, sex difference in chromatin structure and synergistic interaction between HNF4a and COUP-TFII may contribute to the female-specific expression of Cyp3a41 in the livers of mice.
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