| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Outline of Final Research Achievements |
Adipogenesis is controlled by a cascade of transcription factors. The positive feedback loop established by the master regulators PPARγ and C/EBPα is considered to be crucial. Here, we performed ChIP-seq and identified a cluster of multiple distal PPARγ binding sites (+3, +19, +22, +24, +50, +53kb) in downstream region of the Cebpa gene in differentiated 3T3-L1 adipocytes. These clusters of enhancers showed high enrichment of Mediator complex binding and formed a super-enhancer. Furthermore, CTCF－a multifunctional insulator protein which mediates long-range chromatin looping－bound to both distal enhancers and the promoter. 4C-seq and 3C assays demonstrated formation of a chromatin loop encompassing the Cebpa promoter and the distal super-enhancer. Our findings suggest that PPARγ super-enhancer and CTCF-mediated loop formation are important for transactivation of Cebpa gene expression and differentiation.
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