Role of epigenetic regulation on female-predominant expression of drug-metabolizing enzyme CYP3A gene
Project/Area Number |
23590172
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Medical pharmacy
|
Research Institution | University of Toyama |
Principal Investigator |
SAKUMA TSUTOMU 富山大学, 大学院医学薬学研究部(薬学), 准教授 (30250468)
|
Co-Investigator(Kenkyū-buntansha) |
KAWASAKI Yuki 富山大学, 大学院医学薬学研究部(薬学), 助教 (30432107)
|
Project Period (FY) |
2011-04-28 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
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)
|
Keywords | 性差 / CYP / 発現調節 / マウス / エピジェネティック |
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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Report
(5 results)
Research Products
(12 results)