The mechanisms of Environmental Epigenetics

• Project/Area Number: 17H03631
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Molecular biology
• Research Institution: Gunma University
• Principal Investigator: INAGAKI Takeshi 群馬大学, 生体調節研究所, 教授 (10507825)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2017: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: エピゲノム / ヒストンメチル化修飾 / ベージュ脂肪細胞 / 脂肪細胞分化 / 肥満症 / 生活習慣病 / ヒストン脱メチル化酵素 / 脂肪細胞 / エピジェネティクス / JMJD1A / 白色脂肪細胞の褐色化 / ベージュ脂肪

Outline of Final Research Achievements

The environmental factors influence the development of obesity and diabetes mellitus. Environmental stimuli are recorded as epigenetic memory which plays important roles in regulating expression of target genes. We have investigated the epigenetic mechanisms for regulating adipocyte characteristics and elucidated the two-step regulatory mechanism of the histone demethylase JMJD1A. In detail, JMJD1A is recruited to the target genomic loci by forming a protein complex containing DNA-binding transcription factors (step 1) and perform enzyme function to demethylate histone modifications for prolonged adaptation such as beige adipogenesis (step 2).

Academic Significance and Societal Importance of the Research Achievements

肥満症をはじめとする代謝関連疾患の発症・進展には、遺伝要因とともに環境要因が関与する。肥満症と関連の深い白色脂肪は、環境刺激を受けてエネルギー蓄積型からエネルギー消費型へと変化することが知られている。本研究の成果は、エネルギー消費型の脂肪細胞が環境要因によって誘導されるエピゲノム機構のひとつを解明したものであり、肥満症を含む生活習慣病発症の原因となる環境記憶の制御を治療標的とする可能性につながるものである。

Research Products

• [Int'l Joint Research] University of California, San Francisco/Sanford-Burnham Med. Res. Institute(米国)
• [Int'l Joint Research] カリフォルニア大学サンフランシスコ校(米国)
• [Journal Article] Epigenetic regulation of beige adipocyte fate by histone methylation (2019)
  • Author(s): Tanimura K, Suzuki T, Vargas D, Shibata H, Inagaki T
  • Journal Title: Endocrine Journal Volume: 66 Issue: 2 Pages: 115-125
  • DOI: 10.1507/endocrj.EJ18-0442
  • NAID: 130007605367
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access
• [Journal Article] Histone demethylase JMJD1A coordinates acute and chronic adaptation to cold stress via thermogenic phospho-switch. (2018)
  • Author(s): Yohei Abe, Yosuke Fujiwara, Hiroki Takahashi, Yoshihiro Matsumura, Tomonobu Sawada, Shuying Jiang, Ryo Nakaki, Aoi Uchida, Noriko Nagao, Makoto Naito, Shingo Kajimura, Hiroshi Kimura, Timothy F. Osborne, Hiroyuki Aburatani, Tatsuhiko Kodama, Takeshi Inagaki, Juro Sakai
  • Journal Title: Nature Communications Volume: 9 Issue: 1 Pages: 1566-1566
  • DOI: 10.1038/s41467-018-03868-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Histone demethylases regulate adipocyte thermogenesis (2018)
  • Author(s): Inagaki Takeshi
  • Journal Title: Diabetology International Volume: 9(4) Issue: 4 Pages: 215-223
  • DOI: 10.1007/s13340-018-0366-y
  • NAID: 130007599037
  • Open Access
• [Journal Article] Zinc transporter ZIP13 suppresses beige adipocyte biogenesis and energy expenditure by regulating C/EBP-β expression. (2017)
  • Author(s): Fukunaka A, Fukada T, Bhin J, Suzuki L, Tsuzuki T, Takamine Y, Bin BH, Yoshihara T, Ichinoseki-Sekine N, Naito H, Miyatsuka T, Takamiya S, Sasaki T, Inagaki T, Kitamura T, Kajimura S, Watada H, Fujitani Y.
  • Journal Title: PLoS Genet. Volume: 13(8) Issue: 8 Pages: 1-23
  • DOI: 10.1371/journal.pgen.1006950
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Regulations of Adipocyte Phenotype and Obesity by IRX3. Positive or Negative? (2017)
  • Author(s): Inagaki T.
  • Journal Title: eBioMedicine Volume: 24 Pages: 7-8
  • DOI: 10.1016/j.ebiom.2017.09.032
  • Open Access
• [Journal Article] T1R3 homomeric sweet taste receptor regulates adipogenesis through Gas-mediated microtubules disassembly and Rho activation in 3T3-L1 cells (2017)
  • Author(s): Y. Masubuchi, Y. Nakagawa, J. Medina, M. Nagasawa, I. Kojima, M. M. Rasenick, T. Inagaki, H. Shibata
  • Journal Title: PLOS ONE Volume: - Issue: 5 Pages: e0176841-e0176841
  • DOI: 10.1371/journal.pone.0176841
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 脂肪の性質制御に関わるヒストン修飾とクロマチン構造の変化 (2019)
  • Author(s): 稲垣 毅
  • Organizer: 第92回内分泌学会学術総会
  • Invited
• [Presentation] Epigenetic adaptation mechanisms of adipocyte by histone methylation (2019)
  • Author(s): 稲垣 毅
  • Organizer: Institute of Cellular and organismic Biology Seminar at Academia Sinica, Taiwan
  • Invited
• [Presentation] 環境記憶のエピゲノム機構 (2019)
  • Author(s): 稲垣 毅
  • Organizer: 第66回北関東医学会総会
  • Invited
• [Presentation] A Chromatin Conformation-Dependent Regulation of Adipocyte Characteristics by JMJD1A (2019)
  • Author(s): 稲垣 毅、酒井寿郎
  • Organizer: 第42回日本分子生物学会年会シンポジウム（Molecular basis of phenotypic variation regulated by epigenome）
  • Invited
• [Presentation] Jmjd1a for beige adipogenesis (2019)
  • Author(s): 稲垣 毅
  • Organizer: RIKEN EPIGENETICS in WAKO (Epigenome Manipulation and Recent Advances in Epigenetics)
  • Invited
• [Presentation] FGF15/FGF19による代謝調節 (2018)
  • Author(s): 稲垣 毅
  • Organizer: 第91回 日本内分泌学会学術総会
  • Invited
• [Presentation] エピゲノムによる代謝の制御と記憶 (2018)
  • Author(s): 稲垣 毅
  • Organizer: 第36回 日本内分泌代謝サマーセミナー
  • Invited
• [Presentation] 脂肪細胞の性質決定に関わるヒストンメチル化修飾 (2018)
  • Author(s): 稲垣 毅
  • Organizer: 第39回日本肥満学会JASSO・APDO joint symposium
  • Int'l Joint Research / Invited
• [Presentation] Epigenetic regulation of adipocyte function (2018)
  • Author(s): 稲垣 毅
  • Organizer: The 13th International Symposium of the Institute Network for Biomedical Sciences
  • Int'l Joint Research / Invited
• [Presentation] 肝の体性幹様細胞を機能肝細胞に効率よく分化誘導する補助肝臓の作成 (2017)
  • Author(s): 小暮公孝、柴田 宏、長澤雅裕、中川祐子、李龍飛、小島至、稲垣 毅、根本雅明、石崎利、桑野博行、幕内雅敏
  • Organizer: 第117回日本外科学会定期学術集会
• [Presentation] マクロファージに発現するT1R3ホモマー甘味受容体の機能 (2017)
  • Author(s): 李龍飛、メディナ ヨハン、長澤雅裕、稲垣 毅、柴田 宏
  • Organizer: 第60回日本糖尿病学会年次学術集会
• [Presentation] ヒストン修飾酵素複合体形成による遺伝子発現調節 (2017)
  • Author(s): 稲垣 毅、阿部陽平、Rozqie Royhan、岩崎 聡、松村欣宏、児玉龍彦、油谷浩幸、酒井寿郎
  • Organizer: 第11回日本エピジェネティクス研究会年会
• [Presentation] 脂肪細胞の機能・性質を制御するエピゲノム機構 (2017)
  • Author(s): 稲垣 毅
  • Organizer: 第16回生体機能研究会
• [Presentation] 脂肪細胞の性質決定に関わるヒストンメチル化制御機構 (2017)
  • Author(s): 稲垣 毅
  • Organizer: 第40回分子生物学会
  • Invited
• [Remarks] 群馬大学生体調節研究所
  • URL: https://www.imcr.gunma-u.ac.jp/
• [Remarks] 群馬大学生体調節研究所代謝エピジェネティクス分野
  • URL: https://epigenetics.imcr.gunma-u.ac.jp/
• [Remarks] 群馬大学生体調節研究所
  • URL: http://www.imcr.gunma-u.ac.jp
• [Remarks] 群馬大学生体調節研究所代謝エピジェネティクス分野
  • URL: http://epigenetics.imcr.gunma-u.ac.jp/en/