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Elucidation of epigenetic mechanisms that memorize inter-tissue communication

Research Project

Project/Area Number 19K06608
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 43050:Genome biology-related
Research InstitutionThe University of Tokyo

Principal Investigator

Matsumura Yoshihiro  東京大学, 先端科学技術研究センター, 准教授 (20375257)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords脂肪組織 / 交感神経系 / 視床下部 / エピゲノム / 代謝制御 / 摂食制御 / 神経 / ヒストン脱メチル化 / ノルアドレナリン / レプチン
Outline of Research at the Start

肥満、2 型糖尿病などの生活習慣病の病因の解明と予防は、超高齢化多死社会をむかえる我が国において大きな課題となっている。本研究では、脂肪組織と神経の情報伝達に着目し、組織間の情報伝達を記憶するエピゲノム(後天的ゲノム修飾)の仕組みを明らかにすることを目的とする。本研究で得られる成果は、メタボリックシンドロームの予防・治療への足がかりとなる。

Outline of Final Research Achievements

The onset of lifestyle-related diseases can be considered to be due to abnormal interactions between tissues mediated by environmental cues. From the analysis of epigenome-modifying enzyme (JMJD1A) knockout mice, this study revealed that 1) epigenome changes are important for inducing the expression of thermogenic genes in white adipose tissue under cold stimulation and 2) the sensitivity of the hypothalamus to leptin secreted from adipose tissue is regulated by the epigenome-modifying enzyme. This study elucidated a part of the inter-tissue communication and epigenome regulation involved in the onset of lifestyle-related diseases.

Academic Significance and Societal Importance of the Research Achievements

エピゲノムは外的環境に依存して後天的に書き換えられる遺伝情報である。生活習慣や食習慣などの環境要因はエピゲノムとして細胞に記憶され、脂肪を蓄積あるいは燃焼しやすい体質を作ったり、食欲の制御に働いていると考えられる。本研究では、脂肪を燃焼する体質がエピゲノムによって制御されること、エピゲノム修飾酵素が食欲の抑制に働いていることを明らかにした。本研究で得られた研究成果は、生活習慣病の予防・治療への足がかりとなる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (18 results)

All 2022 2021 2020 2019

All Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (13 results)

  • [Journal Article] Selective PPARα Modulator Pemafibrate and Sodium-Glucose Cotransporter 2 Inhibitor Tofogliflozin Combination Treatment Improved Histopathology in Experimental Mice Model of Non-Alcoholic Steatohepatitis2022

    • Author(s)
      Murakami K, Sasaki Y, Asahiyama M, Yano W, Takizawa T, Kamiya W, Matsumura Y, Anai M, Osawa T, Fruchart JC, Fruchart-Najib J, Aburatani H, Sakai J, Kodama T, Tanaka T.
    • Journal Title

      Cells

      Volume: 11 Issue: 4 Pages: 720-720

    • DOI

      10.3390/cells11040720

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ubiquitination-dependent and -independent repression of target genes by SETDB1 reveal a context-dependent role for its methyltransferase activity during adipogenesis2021

    • Author(s)
      Zhang J, Matsumura Y, Kano Y, Yoshida A, Kawamura T, Hirakawa H, Inagaki T, Tanaka T, Kimura H, Yanagi S, Fukami K, Doi T, Osborne TF, Kodama T, Aburatani H, Sakai J.
    • Journal Title

      Genes Cells

      Volume: 26 Issue: 7 Pages: 513-529

    • DOI

      10.1111/gtc.12868

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pemafibrate, a selective PPARα modulator, prevents non-alcoholic steatohepatitis development without reducing the hepatic triglyceride content.2020

    • Author(s)
      Sasaki Y, Asahiyama M, Tanaka T, Yamamoto S, Murakami K, Kamiya W, Matsumura Y, Osawa T, Anai M, Fruchart JC, Aburatani H, Sakai J, Kodama T.
    • Journal Title

      Sci Rep

      Volume: 10 Issue: 1 Pages: 7817-7817

    • DOI

      10.1038/s41598-020-64902-8

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PPARα activation directly upregulates thrombomodulin in the diabetic retina.2020

    • Author(s)
      Shiono A, Sasaki H, Sekine R, Abe Y, Matsumura Y, Inagaki T, Tanaka T, Kodama T, Aburatani H, Sakai J, Takagi H.
    • Journal Title

      Sci Rep

      Volume: 10 Issue: 1 Pages: 10837-10837

    • DOI

      10.1038/s41598-020-67579-1

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gene Expression Profiles Induced by a Novel Selective Peroxisome Proliferator-Activated Receptor α Modulator (SPPARMα) Pemafibrate2019

    • Author(s)
      Sasaki Y, Raza-Iqbal S, Tanaka T, Murakami K, Anai M, Osawa T, Matsumura Y, Sakai J, Kodama T
    • Journal Title

      Int J Mol Sci

      Volume: 20(22) Issue: 22 Pages: 5682-5682

    • DOI

      10.3390/ijms20225682

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Thermogenic Gene Inductions via Phosphatase Complex of Histone Demethylase JMJD1A during Beige Adipocyte Differentiation2021

    • Author(s)
      楊歌,高橋宙大,米代武司,楊超然,松村欣宏,酒井寿郎.
    • Organizer
      第94回日本生化学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Signal sensing histone demethylase regulates a concerted thermogenic response in brown adipose tissue and subcutaneous white adipose tissue in animals2021

    • Author(s)
      謝詩雨,伊藤亮,Tumenjargal Myagmar,松村欣宏,米代武司,楊歌,高橋宙大,酒井寿郎
    • Organizer
      第94回日本生化学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Identification of Sirt3 as a JMJD1A target gene that could regulate mitochondria function during beige adipogenesis2021

    • Author(s)
      楊超然,高橋宙大,米代武司,松村欣宏,伊藤亮,酒井寿郎.
    • Organizer
      第94回日本生化学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Histone demethylase JMJD1A regulates innervation in white adipose tissue2021

    • Author(s)
      趙亞楠,伊藤亮,酒井寿郎,松村欣宏,米代武司.
    • Organizer
      第94回日本生化学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] MYPT1-PP1β脱リン酸化酵素複合体による細胞記憶の書き換えを介したベージュ化制御機構の解明2021

    • Author(s)
      高橋宙大,楊歌,米代武司,楊超然,伊藤亮,松村欣宏,酒井寿郎.
    • Organizer
      第44回日本分子生物学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ヒストン脱メチル化酵素と脱リン酸化酵素複合体によるベージュ化制御機構の解明2021

    • Author(s)
      楊歌,神仁美,高橋宙大,伊藤亮,秋葉大地,松村欣宏,酒井寿郎.
    • Organizer
      第44回日本分子生物学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 中枢神経系におけるヒストン脱メチル化酵素JMJD1Aを介した環境適応機構の解明2021

    • Author(s)
      清水佑一,寒河江陽菜,荒井誠,張吉,関根怜生,内田あおい,伊藤亮,松村欣宏,前島裕子,下村健寿,中田正範,酒井寿郎.
    • Organizer
      第44回日本分子生物学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ヒストン脱メチル化酵素JMJD1Aの酵素活性は褐色脂肪組織の熱産生には不要であり白色脂肪組織における熱産生に必要である2021

    • Author(s)
      伊藤亮,謝詩歌,Tumenjargal Myagmar,楊超然,米代武司,松村欣宏,酒井寿郎.
    • Organizer
      第44回日本分子生物学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 脂肪分化におけるエネルギー感知センサーであるヒストン脱メチル化酵素KDM3Aの標的遺伝子及び結合領域のゲノムワイド解析2021

    • Author(s)
      松村欣宏,Eko Fuji Ariyanto,張吉,楊超然,高橋宙大,伊藤亮,米代武司,曽我朋義,酒井寿郎.
    • Organizer
      第44回日本分子生物学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 脂肪細胞分化を制御するヒストンメチル化・脱メチル化反応2021

    • Author(s)
      松村欣宏, Eko Fuji Ariyanto, 曽我朋義, 酒井寿郎
    • Organizer
      第93回 日本生化学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] SETDB1 represses H3K4/H3K9me3 bivalent genes by ubiquitination-dependent and -independent mechanisms2021

    • Author(s)
      張吉, 松村欣宏, 鹿野優佳, 吉田文乃, 川村猛, 平川弘幸, 油谷浩幸, 酒井寿郎
    • Organizer
      第93回 日本生化学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 脂肪細胞における栄養環境の感知とエピゲノムによる代謝制御2019

    • Author(s)
      松村欣宏,Eko Fuji Ariyanto,曽我朋義,酒井寿郎
    • Organizer
      第92回 日本生化学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 脂肪細胞の運命を決定する代謝物質群2019

    • Author(s)
      松村欣宏,Eko Fuji Ariyanto,曽我朋義,酒井寿郎
    • Organizer
      第42回 日本分子生物学会年会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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