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The role of imprinted genes in metabolic regulation and their evolutionary significance.

Research Project

Project/Area Number 19K06607
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 InstitutionGunma University

Principal Investigator

Morita Sumiyo  群馬大学, 生体調節研究所, 助教 (40589264)

Co-Investigator(Kenkyū-buntansha) 堀居 拓郎  群馬大学, 生体調節研究所, 准教授 (00361387)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsゲノムインプリンティング / 白色脂肪 / 褐色脂肪 / インプリンティング / 代謝調節
Outline of Research at the Start

私たちは白色脂肪におけるインプリント遺伝子の発現と体重の関係において、父性発現と母性発現インプリント遺伝子の役割の明らかな差を発見してきた。本研究では、エネルギーを消費し、肥満に関連する褐色脂肪細胞およびベージュ脂肪細胞におけるインプリント遺伝子の発現解析を行い体重との相関を検証する。さらに体重と相関があり、その機能が未知であるインプリント遺伝子のコンディショナルノックアウトマウスを作製し、肥満または痩せに関与するかを調べる。このようにして褐色脂肪、およびベージュ脂肪細胞における代謝調節(熱産生)においてインプリント遺伝子がどのような役割をもつのかを明らかにする。

Outline of Final Research Achievements

In mammals, paternally and maternally derived genomes are not functionally equivalent. This is due to the presence of imprinted genes that are expressed in a paternal- and maternal-derived allele-specific manner. In this study, we analysed the function of imprinted genes in obesity-associated brown and beige adipocytes. Furthermore, conditioned knockout mice of one of the imprinted genes, Meg3, were generated and examined for their involvement in obesity or emaciation. In this way, the role of imprinted genes in metabolic regulation (heat production) in brown and beige adipocytes was clarified and the biological and evolutionary significance of genomic imprinting was discussed.

Academic Significance and Societal Importance of the Research Achievements

多くの哺乳類でみられる褐色脂肪細胞やベージュ脂肪細胞は全身のエネルギー代謝を制御していることが明らかとなってきた。これらの脂肪細胞は活発に熱を産生しエネルギーを消費することから、肥満や生活習慣病の治療標的として極めて注目されている。本研究ではこれらの脂肪細胞におけるインプリント遺伝子の役割を解析することでインプリント遺伝子の生物学的意義を解明するだけでなく、新たに熱産生機能に関与することが明らかとなったインプリント遺伝子は創薬の標的となる可能性をもち、肥満や生活習慣病の新たな治療戦略として活用できるのではないかと考える。

Report

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

    (10 results)

All 2021 2020 2019

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (4 results)

  • [Journal Article] Calcium-Free and Cytochalasin B Treatment Inhibits Blastomere Fusion in 2-Cell Stage Embryos for the Generation of Floxed Mice via Sequential Electroporation2020

    • Author(s)
      Horii T, Kobayashi R, Kimura M, Morita S, Hatada I.
    • Journal Title

      Cells

      Volume: 9 Issue: 5 Pages: 1088-1088

    • DOI

      10.3390/cells9051088

    • NAID

      130007925824

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Successful generation of epigenetic disease model mice by targeted demethylation of the epigenome.2020

    • Author(s)
      Horii T, Morita S, Hino S, Kimura M, Hino Y, Kogo H, Nakao M & Hatada I
    • Journal Title

      Genome Biology

      Volume: 21(1) Issue: 1 Pages: 77-77

    • DOI

      10.1186/s13059-020-01991-8

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synergistic Upregulation of Target Genes by TET1 and VP64 in the dCas9-SunTag Platform.2020

    • Author(s)
      Morita S, Horii T, Kimura M, Hatada I.
    • Journal Title

      Int J Mol Sci.

      Volume: 21 Issue: 5 Pages: 1574-1574

    • DOI

      10.3390/ijms21051574

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Targeted DNA demethylation of the Fgf21 promoter by CRISPR/dCas9-mediated epigenome editing.2020

    • Author(s)
      Hanzawa N, Hashimoto K, Yuan X, Kawahori K, Tsujimoto K, Hamaguchi M, Tanaka T, Nagaoka Y, Nishina H, Morita S, Hatada I, Yamada T, Ogawa Y.
    • Journal Title

      Sci Rep.

      Volume: 10 Issue: 1 Pages: 5181-5181

    • DOI

      10.1038/s41598-020-62035-6

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anephrogenic phenotype induced by SALL1 gene knockout in pigs.2019

    • Author(s)
      Watanabe M, Nakano K, Uchikura A, Matsunari H, Yashima S, Umeyama K, Takayanagi S, Sakuma T, Yamamoto T, Morita S, Horii T, Hatada I, Nishinakamura R, Nakauchi H, Nagashima H.
    • Journal Title

      Sci Rep.

      Volume: 9 Issue: 1 Pages: 8016-8016

    • DOI

      10.1038/s41598-019-44387-w

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] DNA methylation analysis of multiple imprinted DMRs in Sotos syndrome reveals IGF2-DMR0 as a DNA methylation-dependent, P0 promoter-specific enhancer.2019

    • Author(s)
      Watanabe H, Higashimoto K, Miyake N, Morita S, Horii T, Kimura M, Suzuki T, Maeda T, Hidaka H, Aoki S, Yatsuki H, Okamoto N, Uemura T, Hatada I, Matsumoto N, Soejima H.
    • Journal Title

      FASEB J.

      Volume: 34 Issue: 1 Pages: 960-973

    • DOI

      10.1096/fj.201901757r

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 生殖細胞におけるエピゲノム編集の可能性について2021

    • Author(s)
      森田純代、堀居拓郎、木村美香、畑田出穂
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] dCas9-SunTagシステムにおいてTET1とVP64を用いた特定遺伝子の相乗的発現誘導法の開発2020

    • Author(s)
      森田純代、堀居拓郎、木村美香、畑田出穂
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Research-status Report
  • [Presentation] CRISPR/Cas9ゲノム編集を応用したTET1とVP64による特定遺伝子の相乗的発現誘導法の開発2020

    • Author(s)
      森田純代、堀居拓郎、木村美香、畑田出穂
    • Organizer
      第14回 日本エピジェネティクス研究会年会
    • Related Report
      2020 Research-status Report
  • [Presentation] エピゲノム編集:特定のDNAメチル化領域を効率よく操作する方法の開発2019

    • Author(s)
      森田純代、堀居拓郎、木村美香、畑田出穂
    • 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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