Formation of a Super-enhancer Loop Contributes to Transactivation of Cebpa Expression by PPARg during Adipocyte Differentiation
| Project/Area Number |
15K09378
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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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) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| 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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| Keywords | 糖尿病 / 肥満 / 脂肪細胞 / 遺伝子 / 転写制御 / 高次クロマチン構造 / ゲノム編集 / 発生・分化 |
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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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Report
(4 results)
Research Products
(19 results)
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[Presentation] Formation of a Super-Enhancer Loop Contributes to Transactivation of Cebpa Expression by PPARγ during Adipocyte Differentiation (oral presentation)2016
Author(s)
Tomohisa Aoyama, Hironori Waki, Ken-ichi Wakabayashi, Tsuyoshi Inoue, Masahiro Nakamura, Jing Yu, Atsushi Okabe, Shuichi Tsutsumi, Masato Iwabu, Miki Okada-Iwabu, Kohjiro Ueki, Youichiro Wada, Juro Sakai, Hiroyuki Aburatani, Tatsuhiko Kodama, Toshimasa Yamauchi and Takashi Kadowaki
Organizer
American Diabetes Association 76th Scientific Sessions
Place of Presentation
New Orleans, USA
Year and Date
2016-06-11
Related Report
Int'l Joint Research
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[Presentation] Long-Range Transactivation of Cebpa Expression by PPARγ through Distal Enhancers during Adipocyte Differentiation2015
Author(s)
Tomohisa Aoyama, Hironori Waki, Toshimasa Yamauchi, Ken-ichi Wakabayashi, Tsuyoshi Inoue, Masahiro Nakamura, Jing Yu, Takanori Fujita, Masato, Iwabu, Miki Okada-Iwabu, Takuya Sugiyama, Ueki Kohjiro, Youichiro Wada, Shuichi Tsutsumi, Tatsuhiko Kodama, Juro Sakai, Hiroyuki Aburatani and Takashi Kadowaki
Organizer
Keystone Symposia on Diabetes: New Insights into Molecular Mechanisms and Therapeutic Strategies
Place of Presentation
Tokyo, Japan
Year and Date
2015-10-26
Related Report
Int'l Joint Research
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[Presentation] Long-Range Transactivation of C/EBPα Gene Expression by PPARγ through Distal Enhancers during Adipocyte Differentiation2015
Author(s)
Tomohisa Aoyama, Hironori Waki, Toshimasa Yamauchi, Ken-ichi Wakabayashi, Tsuyoshi Inoue, Masahiro Nakamura, Jing Yu, Takanori Fujita, Masato, Iwabu, Miki Okada-Iwabu, Takuya Sugiyama, Ueki Kohjiro, Youichiro Wada, Shuichi Tsutsumi, Tatsuhiko Kodama, Juro Sakai, Hiroyuki Aburatani and Takashi Kadowaki
Organizer
The 8th Asia-Oceania Conference on Obesity
Place of Presentation
Nagoya, Japan
Year and Date
2015-10-03
Related Report
Int'l Joint Research
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