Multiple functions of histone demethylases

• Project/Area Number: 25640098
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Genome biology
• Research Institution: The University of Tokyo
• Principal Investigator: Inagaki Takeshi 東京大学, 先端科学技術研究センター, 特任准教授 (10507825)
• Project Period (FY): 2013-04-01 – 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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ヒストン修飾酵素 / ヒストン脱メチル化酵素 / ＪＭＪＤ１Ａ / 複合体形成 / ＨＤＡＣ / 転写 / ＦＢＸＬ１０ / クロマチン構造 / ヒストン / JMJD1A / JMJD1B / エピゲノム / 脂肪細胞分化 / SIN3A / ヒストン脱アセチル化 / ＳＩＮ３Ａ

Outline of Final Research Achievements

JmjC domain is a demethylase signature motif and most of JmjC-containing-proteins work as histone demethylase. However, in this study, we demonstrated that JmjC-containing proteins also play non-enzymatic roles. Shotgun proteomic analysis using HeLa cells showed that JMJD1A binds to SIN3A complex including ARID1A and histone deacetylase (HDAC) 1. HDAC activity was induced by repressing Jmjd1a expression in multiple cell lines. Based on these findings, we speculated that JmjC-containing-proteins play non-enzymatic roles by forming functional complex to regulate gene expression. This notion is supported by our two findings that JMJD1A regulates chromatin dynamics by forming complex with SWI/SNF and PPARγ in brown adipocytes and that FBXL10 regulates white adipocyte differentiation by forming a novel polycomb repressive complex including RING1B, BCOR, and SKP1. In addition, our data suggested that JMJD1A regulates the expression of long non-coding RNA.

Research Products

• [Journal Article] Transcriptional and epigenetic control of brown and beige adipocyte cell fate and function (2016)
  • Author(s): Inagaki T., Sakai J, Kajimura S.*
  • Journal Title: Nature Reviews Molecular Cell Biology Volume: 掲載確定
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [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] Research perspectives on the regulation and physiological functions of FGF21 and its association with NAFLD. (2015)
  • Author(s): Inagaki T.*
  • Journal Title: Front. Endocrinol. (Lausanne) Volume: 6 Pages: 147-147
  • DOI: 10.3389/fendo.2015.00147
  • Peer Reviewed / Open Access
• [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] PPARβ/δ activation of CD300a controls intestinal immunity. (2014)
  • Author(s): Tanaka T, Tahara-Hanaoka S, Nabekura T, Ikeda K, Jiang S, Tsutsumi S, Inagaki T, Magoori K, Higurashi T, Takahashi H, Tachibana K, Tsurutani Y, Raza S, Anai M, Minami T, Wada Y, Yokote K, Doi T, Hamakubo T, Auwerx J, Gonzalez FJ, Nakajima A, Aburatani H, Naito M, Shibuya A, Kodama T, Sakai J.
  • Journal Title: Sci Rep Volume: 4 Issue: 1 Pages: 5412-5412
  • DOI: 10.1038/srep05412
  • Peer Reviewed / Open Access
• [Presentation] 転写調節因子とクロマチン構造変化を介した糖脂質代謝制御機構の解明 (2016)
  • Author(s): 稲垣 毅
  • Organizer: 第89回日本内分泌学会学術総会
  • Place of Presentation: 京都国際会館 (京都府)
  • Year and Date: 2016-04-09
  • Invited
• [Presentation] 寒冷刺激に応答するクロマチン構造の調節機構 (2015)
  • Author(s): 稲垣 毅
  • Organizer: Adiposcience in Hiroshima 2nd
  • Place of Presentation: Oriental Hotel Hiroshima (広島県)
  • Year and Date: 2015-11-25
  • Invited
• [Presentation] Regulation of Higher-order Chromatin Structure during Thermogenesis in Brown Adipocytes (2015)
  • Author(s): 稲垣 毅、阿部 陽平、Royhan Rozqie、松村 欣宏、梶村 真吾、酒井 寿郎
  • Organizer: The 46th NIPS International Symposium
  • Place of Presentation: Nagoya Congress Center (愛知県)
  • Year and Date: 2015-10-03
  • Int'l Joint Research / Invited
• [Presentation] エピゲノム研究から見た一卵性双生児 (2015)
  • Author(s): 稲垣 毅
  • Organizer: 第 16 回日本内分泌学会関東甲信越支部学術集会
  • Place of Presentation: 幕張メッセ国際会議場 (千葉県)
  • Year and Date: 2015-09-26
  • Invited
• [Presentation] アディポバイオロジーを制御するヒストン脱メチル化酵素JMJD1Aの修飾シグナル (2015)
  • Author(s): 稲垣 毅、阿部 陽平、Royhan Rozqie、松村 欣宏、梶村 真吾、児玉 龍彦、油谷 浩幸、酒井 寿郎
  • Organizer: 第５８回日本糖尿病学会年次学術集会
  • Place of Presentation: 下関市民会館 (山口県)
  • Year and Date: 2015-05-22
  • Invited
• [Presentation] 脂肪細胞における新規エピゲノム制御機構 (2015)
  • Author(s): 稲垣毅、阿部陽平、Rozqie Royhan、松村欣宏、川村猛、仲木竜、鶴谷悠也、谷村恭子、田中十志也、児玉龍彦、油谷浩幸、酒井寿郎
  • Organizer: 第５２回日本臨床分子医学会学術集会
  • Place of Presentation: 京都みやこめっせ (京都府)
  • Year and Date: 2015-04-11
  • Invited
• [Presentation] 脂肪細胞における新規エピゲノム制御機構 (2015)
  • Author(s): 稲垣毅、阿部陽平、Rozqie Royhan、松村欣宏、川村猛、仲木竜、鶴谷悠也、谷村恭子、田中十志也、児玉龍彦、油谷浩幸、酒井寿郎
  • Organizer: 第５２回日本臨床分子医学会学術集会
  • Place of Presentation: 京都みやこめっせ
  • Year and Date: 2015-04-11
  • Invited
• [Presentation] FBXL10によるエピゲノム複合体を介した脂肪細胞分化調節機構 (2014)
  • Author(s): 稲垣 毅、岩崎 聡、松村欣宏、川村 猛、阿部陽平、吉田文乃、中村加奈子、馬郡健太、仲木 竜、田中十志也、児玉龍彦、油谷浩幸、酒井寿郎
  • Organizer: 第37回日本分子生物学会年会 （ワークショップ）
  • Place of Presentation: 横浜市パシフィコ横浜
  • Year and Date: 2014-11-25
• [Presentation] エネルギー代謝を制御するJMJD1Aによる新規のエピゲノム制御機構 (2014)
  • Author(s): 稲垣 毅
  • Organizer: 第１４回 Islet Biology 研究会
  • Place of Presentation: 東京都千代田区都市センター
  • Year and Date: 2014-08-02
  • Invited
• [Presentation] JMJDIA Regulates Metabolic Gene Expression by Mediating Long-Range Genomic Interactions in Response to β-Adrenergic Stimulation (2014)
  • Author(s): 稲垣 毅
  • Organizer: 第４６回日本動脈硬化学会総会・学術集会 (English session)
  • Place of Presentation: 東京都新宿区京王プラザホテル
  • Year and Date: 2014-07-11
  • Invited
• [Presentation] Regulation of energy expenditure mediated by post-transcriptional modifications of Jmjd1a
  • Author(s): 稲垣毅、阿部陽平、鶴谷悠也、ロイハンロズキ、川村猛、、松村欣宏、酒井寿郎
  • Organizer: 第１０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: 東京都新宿区
• [Presentation] エピゲノムと核内受容体を介した代謝調節
  • Author(s): 稲垣 毅
  • Organizer: 糖尿病・内分泌ステップアップセミナー2013
  • Place of Presentation: 長野県松本市
  • Invited
• [Presentation] Fbxl10 controls adipogenesis through inhibiting clonal expansion by forming an epigenetic regulator complex
  • Author(s): 稲垣毅、岩崎聡、川村猛、阿部陽平、吉田文乃、中村加奈子、馬郡健太、田中十志也、松村欣宏、酒井寿郎
  • Organizer: International Symposium on Transcriptional and Metabolism
  • Place of Presentation: 兵庫県淡路島
• [Remarks] 稲垣毅 東京大学代謝医学分野酒井研究室
  • URL: http://www.mm.rcast.u-tokyo.ac.jp/member/inagaki.html
• [Remarks] 東京大学先端科学技術研究センター 研究者プロフィール
  • URL: http://www.rcast.u-tokyo.ac.jp/ja/people/staff-inagaki_takeshi.html
• [Remarks] LSBM 稲垣毅
  • URL: http://www.lsbm.org/staff/inagaki.html
• [Remarks] 稲垣毅 東京大学代謝医学分野酒井研究室
  • URL: http://www.mm.rcast.u-tokyo.ac.jp/member/inagaki.html
• [Remarks] 東京大学先端科学技術研究センター 研究者プロフィール
  • URL: http://www.rcast.u-tokyo.ac.jp/ja/people/staff-inagaki_takeshi.html
• [Remarks] LSBM 稲垣毅
  • URL: http://www.lsbm.org/staff/inagaki.html