Regulation of epigenome via TCA cycle in adipocytes

• Project/Area Number: 26830136
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: System genome science
• Research Institution: The University of Tokyo
• Principal Investigator: Matsumura Yoshihiro 東京大学, 先端科学技術研究センター, 助教 (20375257)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 代謝ネットワーク / エピゲノム / 生活習慣病 / ヒストンメチル化 / 脂肪細胞分化 / TCA回路 / TCAサイクル

Outline of Final Research Achievements

This study reveled that during adipogenesis, the TCA cycle enzyme IDH3, which catalyzes the synthesis of a-ketoglutarate, is induced to elevate cellular a-ketoglutarate level. The elevation of a-ketoglutarate activates histone demethylase KDM4A and facilitates histone demethylation on glycolysis genes. This, in turn, induces glycolysis genes and promotes glycolysis and lipid accumulation. These results suggest that metabolism regulates epigenome during adipogenesis.

Research Products

• [Int'l Joint Research] Sanford-Burnham Med. Res. Insti.(米国)
• [Journal Article] JMJD1A is a signal-sensing scaffold that regulates acute chromatin dynamics via SWI/SNF association for thermogenesis (2015)
  • Author(s): Abe Y, Rozqie R, Matsumura Y, Kawamura T, Nakaki R, Tsurutani Y, Tanimura-Inagaki K, Shiono A, Magoori K, Nakamura K, Ogi S, Kajimura S, Kimura H, Tanaka T, Fukami K, Osborne TF, Kodama T, Aburatani H, Inagaki T, Sakai J.
  • Journal Title: Nat Commun Volume: 6 Issue: 1 Pages: 1-14
  • DOI: 10.1038/ncomms8052
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] H3K4/H3K9me3 Bivalent Chromatin Domains Targeted by Lineage-Specific DNA Methylation Pauses Adipocyte Differentiation. (2015)
  • Author(s): Matsumura, Y., Nakaki, R., Inagaki, T., Yoshida, A., Kano, Y., Kimura, H., Tanaka, T., Tsutsumi, S., Nakao, M., Doi, T., Fukami, K., Osborne, TF., Kodama, T., Aburatani, H., Sakai, J.
  • Journal Title: Molecular Cell Volume: 60 Issue: 4 Pages: 584-596
  • DOI: 10.1016/j.molcel.2015.10.025
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The FBXL10/KDM2B Scaffolding Protein Associates with Novel Polycomb Repressive Complex-1 to Regulate Adipogenesis. (2015)
  • Author(s): Inagaki T, Iwasaki S, Matsumura Y, Kawamura T, Tanaka T, Abe Y, Yamasaki A, Tsurutani Y, Yoshida A, Chikaoka Y, Nakamura K, Magoori K, Nakaki R, Osborne TF, Fukami K, Aburatani H, Kodama T, Sakai J
  • Journal Title: J Biol Chem Volume: 290 Issue: 7 Pages: 4163-77
  • DOI: 10.1074/jbc.m114.626929
  • Peer Reviewed / Open Access
• [Journal Article] JMJD1A is a signal-sensing scaffold that regulates acute chromatin dynamics via SWI/SNF association for thermogenesis. (2015)
  • Author(s): Abe Y, Rozqie R, Matsumura Y, Kawamura T, Nakaki R, Tsurutani Y, Tanimura-Inagaki K, Shiono A, Magoori K, Nakamura K, Ogi S, Kajimura S, Kimura H, Tanaka T, Fukami K, Osborne TF, Kodama T, Aburatani H, Inagaki T, Sakai J
  • Journal Title: Nat Commun Volume: in press
  • Peer Reviewed
• [Presentation] H3K4/H3K9me3 Bivalent Chromatin Domains Targeted by Lineage-Specific DNA Methylation Pauses Adipogenesis (2016)
  • Author(s): Yoshihiro Matsumura, Ryo Nakaki, Takeshi Inagaki, Ayano Yoshida, Yuka Kano, Hiroshi Kimura, Toshiya Tanaka1, Shuichi Tsutsumi, Mitsuyoshi Nakao, Takefumi Doi, Kiyoko Fukami, Timothy F. Osborne, Tatsuhiko Kodama, Hiroyuki Aburatani, Juro Sakai
  • Organizer: Keystone Symposia Chromatin and Epigenetics
  • Place of Presentation: Whistler, British Columbia, Canada
  • Year and Date: 2016-03-20
  • Int'l Joint Research
• [Presentation] 熱産生関連遺伝子の転写制御におけるエンハンサーの機能解析 (2015)
  • Author(s): 小山一貴、阿部陽平、松村欣宏、稲垣毅、酒井寿郎
  • Organizer: 第38回日本分子生物学会年会、第88回日本生化学大会 合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
• [Presentation] ヒストンメチル化酵素SETDB1のユビキチン化修飾 (2015)
  • Author(s): 鹿野優佳、松村欣宏、吉田文乃、柳茂、稲垣毅、酒井寿郎
  • Organizer: 第38回日本分子生物学会年会、第88回日本生化学大会 合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
• [Presentation] Metabolic Regulation of Histone Demethylation and Glycolysis Gene Expression by Isocitrate Dehydrogenase 3 during Adipogenesis (2015)
  • Author(s): Eko F. Ariyanto、松村欣宏、曽我朋義、稲垣毅、酒井寿郎
  • Organizer: 第38回日本分子生物学会年会、第88回日本生化学大会 合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
• [Presentation] SETDY Regulates C/EBP alpha Transcription during Adipogenesis (2015)
  • Author(s): 馬郡健太、山崎あゆむ、大木翔太郎、松村欣宏、稲垣毅、酒井 寿郎
  • Organizer: 第38回日本分子生物学会年会、第88回日本生化学大会 合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
• [Presentation] 細胞系譜特異的DNAメチル化により形成されるH3K4/H3K9me3クロマチンドメインは脂肪細胞分化を停止させる (2015)
  • Author(s): 松村欣宏、吉田文乃、仲木竜、鹿野優佳、稲垣毅、油谷浩幸、酒井寿郎
  • Organizer: 第38回日本分子生物学会年会、第88回日本生化学大会 合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
• [Presentation] Lineage-specific gene-body DNA Methylation and non-canonical H3K4/H3K9me3 bivalent domains maintain adipocyte lineage (2015)
  • Author(s): Yoshihiro Matsumura, Ayano Yoshida, Ryo Nakaki, Ken-ichi Wakabayashi, Takeshi Inagaki, Kiyoko Fukami, Hiroyuki Aburatani, Juro Sakai
  • Organizer: The 40th Naito Conference Epigenetics
  • Place of Presentation: 札幌
  • Year and Date: 2015-09-15
• [Presentation] Lineage-specific Gene Body DNA Methylation Recruits SETDB1 to Form Non-Canonical Bivalent Chromatin Domains That Inhibit Cebpa and Pparg expression and adipogenesis (2015)
  • Author(s): Yoshihiro Matsumura, Ayano Yoshida, Ryo Nakaki, Ken-ichi Wakabayashi, Takeshi Inagaki, Kiyoko Fukami, Hiroyuki Aburatani, Juro Sakai
  • Organizer: Deuel Conference on Lipids
  • Place of Presentation: Monterey, CA, USA
  • Year and Date: 2015-03-03 – 2015-03-06
• [Presentation] Role of Isocitrate Dehydrogenase 3 in Regulation of Epigenome and Transcription during Adipogenesis (2014)
  • Author(s): Eko F Ariyanoto, Yoshihiro Matsumura Tomoyoshi Soga, Takeshi Inagaki, Juro Sakai
  • Organizer: The 37th Annual Meeting of the Molecular Biology Society of Japan
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] SETDB1は新規のクロマチンドメインを形成することでCepbaの転写と脂肪細胞分化を制御する (2014)
  • Author(s): 松村欣宏、吉田文乃、仲木竜、鹿野優佳、若林賢一、稲垣毅、深見希代子、油谷浩幸、酒井寿郎
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] ヒストンメチル化酵素SETDB1のユビキチン化修飾 (2014)
  • Author(s): 鹿野優佳、松村欣宏、吉田文乃、柳茂、稲垣毅、酒井寿郎
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] SETDB1 regulates metabolic switch of preadipocytes to adipocytes through repression of Cebpα (2014)
  • Author(s): 松村欣宏
  • Organizer: 第11回インスリン抵抗性とメタボリックシンドローム研究会
  • Place of Presentation: 東京
  • Year and Date: 2014-07-05 – 2014-07-06
• [Remarks] 寒冷刺激時の体温維持には熱産生遺伝子の高次構造変化が必須
  • URL: http://www.lsbm.org/news/2015/0512.html
• [Remarks] 脂肪細胞の分化を調節する新規のクロマチン構造の解明
  • URL: http://www.lsbm.org/news/2015/1225.html
• [Remarks] FBXL10/KDM2Bタンパクは脂肪細胞分化を制御する
  • URL: http://www.lsbm.org/news/2014/1226.html