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Exploration of DNA methyltransferase accessible region towards elucidation of the mechanisms for genomic imprinting

Research Project

Project/Area Number 26450449
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Integrative animal science
Research InstitutionTokyo University of Agriculture

Principal Investigator

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

Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsDNAメチル化 / 胚発生 / ゲノムインプリンティング / DNAメチル基転移酵素 / インプリンティング / 卵子 / エピジェネティクス / ゲノミックインプリンティング / 発生
Outline of Final Research Achievements

The mechanisms of DNA methylation including genomic imprinting have not been clarified. It remains unknown how and when DNA methylation is catalyzed at specific DNA sequences. DNA methyltransferases DNMT3A2 and its co-factor DNMT3L are essential for genomic imprinting during gametogenesis and co-expression of them is observed only in germ cells. In this study, to obtain better understand the imprinting machinery, transgenic mice in which DNMT3A2 and DNMT3L are consistently expressed were produced. DNA methylation analysis showed that abnormal DNA methylation occurred at least in five regions but not at imprinted regions. In conclusion, DNA methyltransferase accessible regions differ between germ cell and somatic cell linages and unmethylated alleles of imprinted regions are protected against de novo methylation activity during ontogeny.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (34 results)

All 2018 2017 2016 2015 2014 Other

All Int'l Joint Research (2 results) Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 8 results,  Acknowledgement Compliant: 4 results) Presentation (20 results) (of which Int'l Joint Research: 5 results,  Invited: 6 results) Book (1 results) Patent(Industrial Property Rights) (2 results)

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

    • Related Report
      2015 Research-status Report
  • [Int'l Joint Research] Yale University School of Medicine(米国)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Development of fertile mouse oocytes from mitotic germ cells in vitro.2017

    • Author(s)
      Morohaku K, Hirao Y, and Obata Y.
    • Journal Title

      Nat Protoc

      Volume: 12 Issue: 9 Pages: 1817-1829

    • DOI

      10.1038/nprot.2017.069

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reconstitution of mouse oogenesis in a dish from pluripotent stem cells2017

    • Author(s)
      Hayashi Katsuhiko、Hikabe Orie、Obata Yayoi、Hirao Yuji
    • Journal Title

      Nature Protocols

      Volume: 12 Issue: 9 Pages: 1733-1744

    • DOI

      10.1038/nprot.2017.070

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differentiation of Mouse Primordial Germ Cells into Functional Oocytes In Vitro2017

    • Author(s)
      Morohaku K, Hirao Y, Obata Y.
    • Journal Title

      Ann Biomed Eng

      Volume: 印刷中 Issue: 7 Pages: 1608-1619

    • DOI

      10.1007/s10439-017-1815-7

    • NAID

      120006727811

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Reconstitution in vitro of the entire cycle of the mouse female germ line.2016

    • Author(s)
      Hikabe O, Hamazaki N, Nagamatsu G, Obata Y, Hirao Y, Hamada N, Shimamoto S, Imamura T, Nakashima K, Saitou M, Hayashi K
    • Journal Title

      Nature

      Volume: 539 Issue: 7628 Pages: 299-303

    • DOI

      10.1038/nature20104

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Complete in vitro generation of fertile oocytes from mouse primordial germ cells2016

    • Author(s)
      Morohaku K, Tanimoto R, Sasaki K, Kawahara-Miki R, Kono T, Hayashi K, Hirao Y, Obata Y.
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 113 Issue: 32 Pages: 9021-9026

    • DOI

      10.1073/pnas.1603817113

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Developmental competence of oocytes grown <i>in vitro</i>: Has it peaked already?2016

    • Author(s)
      Morohaku K, Hirao Y, Obata Y.
    • Journal Title

      Journal of Reproduction and Development

      Volume: 62 Issue: 1 Pages: 1-5

    • DOI

      10.1262/jrd.2015-148

    • NAID

      130005126322

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Establishment of a Conditional Transgenic System Using the 2A Peptide in the Female Mouse Germline2014

    • Author(s)
      Hara S, Takano T, Ogata M, Yamakami R, Sato Y, Kono T, Obata Y.
    • Journal Title

      Journal of Reproduction and Development

      Volume: 60 Issue: 3 Pages: 250-255

    • DOI

      10.1262/jrd.2013-143

    • NAID

      130003390833

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Forced expression of DNA methyltransferases during oocyte growth accelerates the establishment of methylation imprints but not functional genomic imprinting2014

    • Author(s)
      Hara S, Takano T, Fujikawa T, Yamada M, Wakai T, Kono T, Obata Y
    • Journal Title

      Hum Mol Genet

      Volume: 23(10) Issue: 14 Pages: 1-12

    • DOI

      10.1093/hmg/ddu100

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epigenetic Modification in Mouse Oocytes2014

    • Author(s)
      Obata Y
    • Journal Title

      Journal of Mammalian Ova Research

      Volume: 31 Issue: 3 Pages: 62-69

    • DOI

      10.1274/jmor.31.62

    • NAID

      130004704228

    • ISSN
      1341-7738, 1347-5878
    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] CRISPR/Cas9システムによる 新規KRAB-ZFP遺伝子機能欠損マウスの作製とその表現型解析2018

    • Author(s)
      府川夏実、佐々木恵亮、尾畑やよい
    • Organizer
      第13回日本生殖発生医学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Parental origin-derived primary memories are erased in Zfp57-deficient embryonic stem cells.2017

    • Author(s)
      Sasaki K, Nakajima A, Morohaku K, Hara H, Asanuma Y, Sotomaru Y, Kono T, and Obata Y.
    • Organizer
      4th World Congress of Reproductive Biology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マウス始原生殖細胞から卵子を産生する新規in vitro系の開発2016

    • Author(s)
      尾畑やよい、平尾雄二
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Dlk1-Dio3ドメインBAC TGマウスの致死性に対するmiRNAの影響2016

    • Author(s)
      隈本宗一郎、雉岡めぐみ、高橋望、外丸祐介、小川英彦、尾畑やよい、河野友宏
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] Complete in vitro generation of fertile oocytes from mouse primordial germ cells2016

    • Author(s)
      Hirao Y, Obata Y
    • Organizer
      2016 ART World Congress
    • Place of Presentation
      New York (USA)
    • Year and Date
      2016-10-13
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Dlk1-Dio3ドメインBAC TGマウスにおける網羅的miRNA発現解析2016

    • Author(s)
      隈本宗一郎、雉岡めぐみ、高橋望、外丸祐介、小川英彦、尾畑やよい、河野友宏
    • Organizer
      第109回日本繁殖生物学会
    • Place of Presentation
      麻布大学(神奈川県相模原市)
    • Year and Date
      2016-09-11
    • Related Report
      2016 Research-status Report
  • [Presentation] マウス胎仔卵巣のガラス化保存と体外培養による始原生殖細胞の高度利用技術の開発2016

    • Author(s)
      諸白家奈子、谷本連、佐々木恵亮、林克彦、平尾雄二、尾畑やよい
    • Organizer
      第109回日本繁殖生物学会
    • Place of Presentation
      麻布大学(神奈川県相模原市)
    • Year and Date
      2016-09-11
    • Related Report
      2016 Research-status Report
  • [Presentation] マウス始原生殖細胞を成熟卵子へと誘導する新規培養系の開発2016

    • Author(s)
      有冨大輝、武田久美子、尾畑やよい、平尾雄二
    • Organizer
      第109回日本繁殖生物学会
    • Place of Presentation
      麻布大学(神奈川県相模原市)
    • Year and Date
      2016-09-11
    • Related Report
      2016 Research-status Report
  • [Presentation] ステロイドホルモン受容体の制御がin vitroにおけるマウス卵胞形成に果たす役割2016

    • Author(s)
      谷本連、諸白家奈子、河野友宏、平尾雄二、尾畑やよい
    • Organizer
      第109回日本繁殖生物学会
    • Place of Presentation
      麻布大学(神奈川県相模原市)
    • Year and Date
      2016-09-11
    • Related Report
      2016 Research-status Report
  • [Presentation] Abnormal Follicle Assembly In Vitro Correlates with Ectopic Expression of Amh in Mice2016

    • Author(s)
      Tanimoto R, Morohaku K, Sasaki K, Kawahara-Miki R, Kono T, Hayashi K, Hirao Y, Obata Y.
    • Organizer
      49th Annual Meeting of Society for the Study of Reproduction
    • Place of Presentation
      San Diego (USA)
    • Year and Date
      2016-07-16
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] in vitroにおいて産生されたマウス卵の発生能2015

    • Author(s)
      尾畑やよい、平尾雄二
    • Organizer
      第108回日本繁殖生物学会シンポジウム
    • Place of Presentation
      宮崎大学
    • Year and Date
      2015-09-17
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] in vitroで分化したマウス胎仔卵巣における網羅的遺伝子発現解析2015

    • Author(s)
      谷本連、諸白家奈子、河野友宏、平尾雄二、尾畑やよい
    • Organizer
      第108回日本繁殖生物学会
    • Place of Presentation
      宮崎大学
    • Year and Date
      2015-09-17
    • Related Report
      2015 Research-status Report
  • [Presentation] 胚発生過程においてDNAメチル化酵素がアクセス可能な遺伝子座のスクリーニング2015

    • Author(s)
      佐々木恵亮、原聡史、山上怜奈、竹内秀斗、長谷川 沙紀、小肩実央、河野友宏、尾畑やよい
    • Organizer
      第108回日本繁殖生物学会
    • Place of Presentation
      宮崎大学
    • Year and Date
      2015-09-17
    • Related Report
      2015 Research-status Report
  • [Presentation] in vitroにおける機能的卵母細胞の作出2015

    • Author(s)
      尾畑やよい、平尾雄二
    • Organizer
      第36回日本炎症・再生医学会シンポジウム
    • Place of Presentation
      虎の門ヒルズフォーラム
    • Year and Date
      2015-07-21
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] In vitro growth of primordial follicles derived from neonatal mouse ovaries2015

    • Author(s)
      Morohaku K, Kono T, Hirao Y, Obata Y.
    • Organizer
      Gordon Research Conference 2015, Fertilization & Activation of Development
    • Place of Presentation
      Holderness, NH, USA
    • Year and Date
      2015-07-19
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Ectopic expression of DNMT3A2 and DNMT3L during embryogenesis leads to abnormal methylations at certain gene promoters but not at the imprinted loci2015

    • Author(s)
      Sasaki K, Hara S, Yamakami R, Takeuchi S, Hasegawa S, Ogata M, Kono T, Obata Y.
    • Organizer
      Gordon Research Conference 2015, Fertilization & Activation of Development
    • Place of Presentation
      Holderness, NH, USA
    • Year and Date
      2015-07-19
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] in vitroにおける卵母細胞の成長・成熟2015

    • Author(s)
      尾畑やよい
    • Organizer
      第60回日本生殖医学会シンポジウム
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2015-04-27
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] DNAメチル化による卵子特異的インプリントの確立機構2014

    • Author(s)
      尾畑やよい
    • Organizer
      第59回 日本生殖医学会
    • Place of Presentation
      京王プラザホテル(東京都新宿区)
    • Year and Date
      2014-12-04 – 2014-12-05
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 新生仔マウス由来卵胞から体外培養で得られた卵の発生能解析2014

    • Author(s)
      諸白家奈子、平尾雄二、河野友宏、尾畑やよい
    • Organizer
      第107回 日本繁殖生物学会
    • Place of Presentation
      帯広畜産大学
    • Year and Date
      2014-08-20 – 2014-08-24
    • Related Report
      2014 Research-status Report
  • [Presentation] DNAメチル基転移酵素過剰発現により卵母細胞で早期に誘導されたメチル化インプリントの機能2014

    • Author(s)
      尾畑やよい、原 聡史、河野友宏
    • Organizer
      第55回 日本卵子学会
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2014-05-17 – 2014-05-18
    • Related Report
      2014 Research-status Report
  • [Book] 哺乳動物の発生工学(「発生学とエピジェネティクス」)2014

    • Author(s)
      編者 4名 著 尾畑やよい 他12名
    • Total Pages
      200
    • Publisher
      朝倉書店
    • Related Report
      2014 Research-status Report
  • [Patent(Industrial Property Rights)] 始原生殖細胞を機能的に成熟した卵母細胞へと分化させる培養方法2016

    • Inventor(s)
      尾畑やよい、平尾雄二、林克彦
    • Industrial Property Rights Holder
      東京農業大学、農業・食品産業技術総合研究機構、九州大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016-09-16
    • Related Report
      2016 Research-status Report
  • [Patent(Industrial Property Rights)] 始原生殖細胞を機能的に成熟した卵母細胞へと分化させる培養方法2015

    • Inventor(s)
      尾畑やよい、平尾雄二、林克彦
    • Industrial Property Rights Holder
      東京農業大学、農業・食品産業技術研究総合研究機構、九州大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-09-17
    • Related Report
      2015 Research-status Report

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Published: 2014-04-04   Modified: 2022-01-27  

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