| Project/Area Number |
25860742
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Metabolomics
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 遺伝子 / 転写制御 / 高次クロマチン構造 / 3C / 脂肪細胞 / 分化 / 糖尿病 / 肥満 / 発生・分化 / 遺伝子発現制御 |
|---|
| Outline of Final Research Achievements |
Adipogenesis is controlled by a cascade of transcription factors. Although the positive feedback loop established by the master regulators PPARγ and C/EBPα is crucial, the precise mechanism by which PPARγ regulates Cebpa gene expression remains elusive. Here, we performed ChIP-seq using PPARγ antibodies and identified specific functional enhancers in the distal downstream region of the Cebpa gene in differentiated 3T3-L1 adipocytes. These regions exhibited increased histone H3 acetylation and chromatin accessibility (as judged by FAIRE-qPCR) during differentiation. 3C (Chromosome Conformation Capture) assays revealed physical interactions between these distal enhancers and the promoter of the Cebpa gene, which were enhanced upon differentiation. Our findings suggest that transactivation of C/EBPα expression by PPARγ involves distal enhancers, long-range DNA looping and hierarchical epigenetic changes.
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