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Epigenetics of trophoblast and embryonic stem cells by a novel histone-glycosylation

Research Project

Project/Area Number 26252052
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Integrative animal science
Research InstitutionWaseda University (2015-2016)
The University of Tokyo (2014)

Principal Investigator

Shiota Kunio  早稲田大学, 理工学術院, 上級研究員(研究院教授) (80196352)

Co-Investigator(Kenkyū-buntansha) 廣澤 瑞子  東京大学, 農学生命科学研究科, 助教 (60533982)
新井 大祐  早稲田大学, 理工学術院, 次席研究員(研究院講師) (20624951)
早川 晃司  東京大学, 大学院農学生命科学研究科(農学部), 特任助教 (50636800)
Project Period (FY) 2014-06-27 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥40,170,000 (Direct Cost: ¥30,900,000、Indirect Cost: ¥9,270,000)
Fiscal Year 2016: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
Fiscal Year 2015: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000)
Fiscal Year 2014: ¥15,080,000 (Direct Cost: ¥11,600,000、Indirect Cost: ¥3,480,000)
Keywordsエピジェネティクス / ヒストン修飾 / H2A-アセチルグルコサミン(GlcNAc)修飾 / ゲノム修復 / グルコース感受性 / 栄養膜幹細胞 / 胚性幹細胞 / 進化 / Nアセチルグルコサミン(GlcNAc) / ゲノムダメージ / グリコシル化 / ゲノムワイド
Outline of Final Research Achievements

We discovered O-linked-N-acetylglucosamine (O-GlcNAc) modification of histone H2A at Serine 40 (H2AS40Gc). The H2AS40Gc site is in the L1 loop structure where two H2A molecules interact in the nucleosome. The novel O-GlcNAcylation is specific to the Serine 40 isoforms, which emerged in Marsupialia and persisted thereafter in mammals. Targets of H2AS40Gc are distributed genome-wide and are dramatically changed during the differentiation in mouse trophoblast stem cells. The level of H2AS40Gc is also responsive to glucose level and DNA damage. Intriguingly, hyper-H2AS40Gc induced by changing glucose level or the overexpression of the H2A3 Serine 40 isoform protected the genome from DNA damage in mouse embryonic stem cells. Thus the H2AS40Gc functions DNA damage repair. Based on these data, the emergence of H2A Serine 40 and its O-GlcNAcylation linked a genetic event to genome-wide epigenetic events that correlate with the evolution of placental animals.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report

Research Products

(28 results)

All 2017 2016 2015 2014 Other

All Int'l Joint Research (2 results) Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (12 results) (of which Invited: 6 results) Remarks (1 results) Patent(Industrial Property Rights) (4 results) (of which Overseas: 2 results)

  • [Int'l Joint Research] Albert Einstein College of Medicine/University of Wisconsin-Madison(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] Institut Albert Bonniot(グルノーブル大学)(フランス)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Novel O-GlcNAcylation on Ser40 of canonical H2A isoforms specific to viviparity.2016

    • Author(s)
      Hirosawa M, Hayakawa K, Yoneda C, Arai D, Shiota H, Suzuki T, Tanaka S, Dohmae N, Shiota K.
    • Journal Title

      Sci Rep

      Volume: 6

    • DOI

      10.1038/srep31785

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Linker histone variant H1T targets rDNA repeats.2016

    • Author(s)
      Tani R, Hayakawa K, Tanaka S, Shiota K.
    • Journal Title

      Epigenetics

      Volume: 11(4) Pages: 288-302

    • DOI

      10.1080/15592294.2016.1159369

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Putative Epimutagens in Maternal Peripheral and Cord Blood Samples Identified Using Human Induced Pluripotent Stem Cells.2015

    • Author(s)
      Arai Y, Hayakawa K, Arai D, Ito R, Iwasaki Y, Saito K, Akutsu K, Takatori S, Ishii R, Hayashi R, Izumi S, Sugino N, Kondo F, Horie M, Nakazawa H, Makino T, Hirosawa M, Shiota K, Ohgane J.
    • Journal Title

      Biomed Res Int

      Volume: 2015 Pages: 1-13

    • DOI

      10.1155/2015/876047

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Isolation and manipulation of mouse trophoblast stem cells2015

    • Author(s)
      Hayakawa K, Himeno E, Tanaka S, Kunath T.
    • Journal Title

      Curr Protoc Stem Cell Biol

      Volume: 32 Pages: 1-32

    • DOI

      10.1002/9780470151808.sc01e04s32

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Diabetes Induces Aberrant DNA Methylation in the Proximal Tubules of the Kidney.2015

    • Author(s)
      Marumo T, Yagi S, Kawarazaki W, Nishimoto M, Ayuzawa N, Watanabe A, Ueda K, Hirahashi J, Hishikawa K, Sakurai H, Shiota K, Fujita T.
    • Journal Title

      J Am Soc Nephrol.

      Volume: 印刷中

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An epigenetic regulatory element of the Nodal gene in the mouse and human genomes.2015

    • Author(s)
      Arai D, Hayakawa K, Ohgane J, Hirosawa M, Nakao Y, Tanaka S, Shiota K.
    • Journal Title

      Mech Dev.

      Volume: 136 Pages: 143-154

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] N-Acetylmannosamine improves sleep-wake quality in middle-aged mice: relevance to autonomic nervous function.2015

    • Author(s)
      Kuwahara M, Ito K, Hayakawa K, Yagi S, Shiota K.
    • Journal Title

      Auton Neurosci.

      Volume: 187 Pages: 56-62

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] RNA-seq analysis of equine conceptus transcripts during embryo fixation and capsule disappearance.2014

    • Author(s)
      Tachibana Y, Sakurai T, Bai H, Shiota K, Nambo Y, Nagaoka K, Imakawa K.
    • Journal Title

      PLoS One

      Volume: 9(12)

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DNA methylation and its role in the trophoblast cell lineage.2014

    • Author(s)
      Tanaka S, Nakanishi MO, Shiota K.
    • Journal Title

      Int J Dev Biol.

      Volume: 58(2-4) Pages: 231-238

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Presentation] H2AS40-GlcNAc modification specific to placental animals2017

    • Author(s)
      塩田邦郎
    • Organizer
      RIKEN Epigenetics 2017
    • Place of Presentation
      理研バイオリソースセンター(茨城)
    • Year and Date
      2017-02-17
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 新たなヒストンH2A-GlcNAc修飾:Canonical Subtypes vs. Variants2017

    • Author(s)
      塩田邦郎
    • Organizer
      第4回ヒストンバリアント研究会
    • Place of Presentation
      東北大学青葉山キャンパス(宮城)
    • Year and Date
      2017-02-11
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] ヒストンH2AのL1領域におけるアイソフォーム特異的な新規O-GlcNAc修飾2016

    • Author(s)
      廣澤瑞子・早川晃司・米田智佳子・新井大祐・塩田仁志・鈴木健裕・田中智・堂前直・塩田邦郎
    • 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)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] ヒストンH2A O-GlcNAc修飾による哺乳類特有DNA修復機構2016

    • Author(s)
      早川晃司・廣澤瑞子・谷瑠依子・米田智佳子・田中智・塩田邦郎
    • 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)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] 糖による新たなヒストン修飾を発見2016

    • Author(s)
      廣澤瑞子
    • Organizer
      平成28年度農学系研究科研究交流会
    • Place of Presentation
      東京大学農学部弥生講堂アネックス(東京)
    • Year and Date
      2016-11-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] 日本食評価エピジェネティクス研究:その魅力とその実証に向けて2016

    • Author(s)
      塩田邦郎
    • Organizer
      第3回みそサイエンス研究会総会
    • Place of Presentation
      マリオット銀座東武ホテル(東京)
    • Year and Date
      2016-06-07
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Epigenetic switching by hexosamine biosynthesis pathway2015

    • Author(s)
      Kunio Shiota
    • Organizer
      Seminar in the reproduction series in Cornell University
    • Place of Presentation
      イサカ、アメリカ
    • Year and Date
      2015-03-11
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Glucose causes neurodegeneration in induced orexin neurons2014

    • Author(s)
      Koji Hayakawa,Kunio Shiota
    • Organizer
      The 2014 ASCB/IFCB meeting
    • Place of Presentation
      フィラデルフィア、アメリカ
    • Year and Date
      2014-12-06 – 2014-12-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] O-linked N-acetylglucosamine transderase accumulates at Mgea5, β-N-acetylglucosaminidase gene loci in mouse trophoblast stem cell2014

    • Author(s)
      Kenta Nishitani, Koji Hayakawa, Mitusko HIrosawa, Satoshi Tanaka, Kunio Shiota
    • Organizer
      The 2014 ASCB/IFCB meeting
    • Place of Presentation
      フィラデルフィア、アメリカ
    • Year and Date
      2014-12-06 – 2014-12-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] The influence of glucose concentration on the pluripotency of mouse embryonic stem cells2014

    • Author(s)
      Chikako Yoneda, Koji Hayakawa, Mitsuko Hirosawa, Satoshi Tanaka, Kunio Shiota
    • Organizer
      The 2014 ASCB/IFCB meeting
    • Place of Presentation
      フィラデルフィア、アメリカ
    • Year and Date
      2014-12-06 – 2014-12-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] 単糖によるオレキシン神経誘導の多重エピジェネティック制御2014

    • Author(s)
      早川 晃司
    • Organizer
      第87回 日本生化学会大会
    • Place of Presentation
      国立京都国際会館、京都
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 代謝を感知するゲノム制御・GlycoEpigeneticの展開2014

    • Author(s)
      塩田 邦郎
    • Organizer
      東京理科大学生命科学研究所セミナー
    • Place of Presentation
      東京理科大学、千葉
    • Year and Date
      2014-10-09
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Remarks] 胎生動物出現の鍵 : 糖による新たなエピジェネティック修飾を発見

    • URL

      http://www.a.u-tokyo.ac.jp/topics/2016/20160912-1.html

    • Related Report
      2016 Annual Research Report
  • [Patent(Industrial Property Rights)] グルコース感受性細胞の保護剤2016

    • Inventor(s)
      塩田邦郎、早川晃司、廣澤ー高森瑞子、藤井遼介、伊藤幸成
    • Industrial Property Rights Holder
      塩田邦郎、早川晃司、廣澤ー高森瑞子、藤井遼介、伊藤幸成
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016-04-01
    • Related Report
      2016 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 糖感知エピゲノムバイオマーカー2016

    • Inventor(s)
      塩田邦郎、廣澤瑞子、早川晃司
    • Industrial Property Rights Holder
      塩田邦郎、廣澤瑞子、早川晃司
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016-09-08
    • Related Report
      2016 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 糖感知エピゲノムバイオマーカー2015

    • Inventor(s)
      塩田邦郎・廣澤瑞子・早川晃司
    • Industrial Property Rights Holder
      塩田邦郎・廣澤瑞子・早川晃司
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-09-09
    • Related Report
      2015 Annual Research Report
  • [Patent(Industrial Property Rights)] グルコース感受性細胞の保護剤2015

    • Inventor(s)
      塩田邦郎・早川晃司・廣澤瑞子・藤井遼介・伊藤幸成
    • Industrial Property Rights Holder
      塩田邦郎・早川晃司・廣澤瑞子・藤井遼介・伊藤幸成
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-04-03
    • Related Report
      2015 Annual Research Report

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Published: 2014-11-20   Modified: 2022-01-28  

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