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Analysis of maternal-derived epigenetic modifications essential for mammalian development

Research Project

Project/Area Number 18H02355
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 42030:Animal life science-related
Research InstitutionTokyo University of Agriculture

Principal Investigator

OBATA Yayoi  東京農業大学, 生命科学部, 教授 (70312907)

Co-Investigator(Kenkyū-buntansha) 樋浦 仁  東京農業大学, 生命科学部, 准教授 (70451523)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Keywords卵子 / エピジェネティック修飾 / miRNA / エピジェネティクス / 胚発生 / 卵子形成 / 卵子形成過程
Outline of Final Research Achievements

Female germ cell, oocyte, is responsible for transmitting to the embryo not only genetic information but also epigenetic modification. Since lack of normal epigenetic modifications in the oocyte lead to embryonic lethality or postnatal disorders, it is essential for functional oocytes to establish epigenetic modifications during oocyte growth. However, there are many enzymes that catalyse epigenetic modifications and it is not easy to achieve multiple deletions of enzymes in oocytes by conventional knockout technology. In this study, we established a method for loss-of-function of multiple enzymes involved in epigenetic modification. This will help to elucidate the mechanisms underlying establishment of maternal epigenetic control mechanisms essential for mammalian embryogenesis.

Academic Significance and Societal Importance of the Research Achievements

親は子に卵子や精子を介して遺伝子やエピジェネティック修飾と呼ばれる遺伝外情報を伝える。エピジェネティック修飾とは、メチル化など可逆的な化学反応で遺伝子を修飾する現象で、卵子や精子のエピジェネティック修飾の異常は、流産や出生後の疾患を引き起こす。そのため、精子や卵子が正常なエピジェネティック修飾を保持することは重要であるが、その機構は十分に理解されていない。その原因として、エピジェネティック修飾を担う酵素が多岐にわたり、多重遺伝子欠損マウスを作ることが困難なためである。本研究では、人工的に設計した小分子RNAによって、卵子で複数のエピジェネティック修飾酵素の機能を喪失させる方法を開発した。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (19 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (2 results) Journal Article (7 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 7 results,  Open Access: 5 results) Presentation (9 results) (of which Invited: 1 results) Remarks (1 results)

  • [Int'l Joint Research] Max Planck Institute(ドイツ)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Yale University School of Medicine(米国)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Oocyte-specific gene knockdown by intronic artificial microRNAs driven by <i>Zp3</i> transcription in mice2021

    • Author(s)
      Sasaki K, Takaoka S, Obata Y
    • Journal Title

      Journal of Reproduction and Development

      Volume: 67 Issue: 3 Pages: 229-234

    • DOI

      10.1262/jrd.2020-146

    • NAID

      130008055064

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dnmt3a2/Dnmt3L Overexpression in the Dopaminergic System of Mice Increases Exercise Behavior through Signaling Changes in the Hypothalamus2020

    • Author(s)
      Cui D, Mesaros A, Burdeos G, Voigt I, Giavalisco P, Hinze Y, Purrio M, Neumaier B, Drzezga A, Obata Y, Endepols H, Xu X
    • Journal Title

      Int J Mol Sci

      Volume: 21 Issue: 17 Pages: 6297-6297

    • DOI

      10.3390/ijms21176297

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Chromatin Protein PC4 Orchestrates B Cell Differentiation by Collaborating with IKAROS and IRF42020

    • Author(s)
      Ochiai Kyoko、Yamaoka Mari、Swaminathan Amrutha、Shima Hiroki、Hiura Hitoshi、Matsumoto Mitsuyo、Kurotaki Daisuke、Nakabayashi Jun、Funayama Ryo、Nakayama Keiko、Arima Takahiro、Ikawa Tomokatsu、Tamura Tomohiko、Sciammas Roger、Bouvet Philippe、Kundu Tapas K.、Igarashi Kazuhiko
    • Journal Title

      Cell Reports

      Volume: 33 Issue: 12 Pages: 108517-108517

    • DOI

      10.1016/j.celrep.2020.108517

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 哺乳類の卵子を体外で産生する2019

    • Author(s)
      諸白家奈子、尾畑やよい
    • Journal Title

      生物工学会誌

      Volume: 97 Pages: 212-212

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ectopic expression of DNA methyltransferases DNMT3A2 and DNMT3L leads to aberrant hypermethylation and postnatal lethality in mice2019

    • Author(s)
      Sasaki Keisuke、Hara Satoshi、Yamakami Reina、Sato Yusuke、Hasegawa Saki、Kono Tomohiro、Morohaku Kanako、Obata Yayoi
    • Journal Title

      Molecular Reproduction and Development

      Volume: 印刷中 Issue: 6 Pages: 614-623

    • DOI

      10.1002/mrd.23137

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 哺乳動物の卵子を体外で産生する2019

    • Author(s)
      諸白家奈子、尾畑やよい
    • Journal Title

      生物工学会誌

      Volume: 97 Pages: 212-212

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of four imprinting disorders and ART2019

    • Author(s)
      Hattori H, Hiura H, Kitamura A, Miyauchi N, Kobayashi N, Takahashi S, Okae H, Kyono K, Kagami M, Ogata T, Arima T.
    • Journal Title

      Clin Epigenetics

      Volume: 11 Issue: 1 Pages: 21-21

    • DOI

      10.1186/s13148-019-0623-3

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Y染色体の存在がマウス雌性生殖系列に及ぼす影響2020

    • Author(s)
      佐藤義治、坂下陽彦、神田暁史、河野友宏、外丸祐介、尾畑やよい
    • Organizer
      日本繁殖生物学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] マウス胎仔卵巣培養のための完全合成培地の構築にむけて2020

    • Author(s)
      木村覚、池田晋也、荒井美希、吉田幸太郎、尾畑やよい
    • Organizer
      日本卵子学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 卵母細胞特異的遺伝子ノックダウンシステムの開発2019

    • Author(s)
      佐々木恵亮、尾畑やよい
    • Organizer
      日本分子生物学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 合成培地におけるin vitroマウス卵子形成2019

    • Author(s)
      木村覚、池田晋也、尾畑やよい
    • Organizer
      日本分子生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 卵母細胞特異的ノックダウンシステムの確立2019

    • Author(s)
      佐々木恵亮、高岡沙綾、尾畑やよい
    • Organizer
      日本繁殖生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] レトロトランスポゾンの脱抑制がマウス前精原細胞の遺伝子発現制御に与える影響2019

    • Author(s)
      池田晋也、田中康貴、大谷麗子、飯田有紀、樋浦仁、外丸祐介、尾畑やよい、河野友宏
    • Organizer
      日本繁殖生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] インプリンティング疾患と生殖補助医療のリスク要因2019

    • Author(s)
      服部裕充、樋浦仁、北村茜、宮内尚子、小林記緒、高橋聡太、岡江寛明、京野廣一、鏡雅代、緒方勤、有馬隆博
    • Organizer
      日本生殖発生医学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] マウス始原生殖細胞で発現するsmall RNA2018

    • Author(s)
      高島友弥、横田将、樋浦仁、小林久人、尾畑やよい、小川英彦、河野友宏
    • Organizer
      日本分子生物学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 体外成長卵母細胞から作出したマウス2細胞期胚のトランスクリプトーム解析2018

    • Author(s)
      藤丸翼、谷本連、小林久人、河野友宏、尾畑やよい
    • Organizer
      日本繁殖生物学会
    • Related Report
      2018 Annual Research Report
  • [Remarks] 東京農業大学HP

    • URL

      https://www.nodai.ac.jp/academics/life_sci/bio/lab/505/

    • Related Report
      2019 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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