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Genome imprinting mechanism based on the chromatin higher order structure

Research Project

Project/Area Number 17K07248
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Genome biology
Research InstitutionNational Center for Child Health and Development

Principal Investigator

Tomikawa Junko  国立研究開発法人国立成育医療研究センター, 周産期病態研究部, 研究員 (80534990)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsアレル特異的ループ形成 / Grb10 / シスエレメント / アレル特異的ループ構造 / CTCF / アレル特異的 / SNPsplit / 片アレル型オープンクロマチン / 両アレル型オープンクロマチン / ゲノム / 発現制御
Outline of Final Research Achievements

Using mouse ES cell line, we analyzed allele-specific epigenomic profile including gene expression, histone modification and chromatin loop conformation. Comparative analysis of genome-wide chromatin loop formation showed that no marked differentiations were observed between maternal and paternal alleles. However, the locus of already-known imprinting gene, Grb10, showed maternal-specific expression and maternal-specific loop formation between the major promoter and a region in which H3K27ac and H3K4me1 modifications were found. We then made the knockout mice lacking the region with H3K27ac and H3K4me1 modifications and investigated the phenotypes of the knockout mice.

Academic Significance and Societal Importance of the Research Achievements

ゲノムインプリンティングは哺乳動物の発生や発育に重要な働きをしており、そのエピジェネティック制御機構の破綻はヒトでは先天異常や癌の発生に関与することが知られている。また、インプリント遺伝子はありふれた(罹患率の高い)疾患にも関与することが示唆されている。例えば、近年の全ゲノム関連解析で、複数の糖尿病感受性SNPがインプリント遺伝子クラスター内に同定されている。マウス細胞をモデル系としてインプリント遺伝子発現に関与するシスエレメントを同定することで、このような疾患感受性SNPの機能推定が可能となると期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (9 results)

All 2020 2019 2018 2017

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (4 results)

  • [Journal Article] Epitranscriptomic profiling in human placenta: N6‐methyladenosine modification at the 5′‐untranslated region is related to fetal growth and preeclampsia2020

    • Author(s)
      Taniguchi Kosuke、Kawai Tomoko、Kitawaki Jo、Tomikawa Junko、Nakabayashi Kazuhiko、Okamura Kohji、Sago Haruhiko、Hata Kenichiro
    • Journal Title

      The FASEB Journal

      Volume: 34 Issue: 1 Pages: 494-512

    • DOI

      10.1096/fj.201900619rr

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Conditional Kisspeptin Neuron-Specific Kiss1 Knockout With Newly Generated Kiss1-floxed and Kiss1-Cre Mice Replicates a Hypogonadal Phenotype of Global Kiss1 Knockout Mice2020

    • Author(s)
      Kana Ikegami, Teppei Goto, Sho Nakamura, Youki Watanabe, Arisa Sugimoto, Sutisa Majarune, Kei Horihata, Mayuko Nagae, Junko Tomikawa, Takuya Imamura, Makoto Sanbo, Masumi Hirabayashi, Naoko Inoue, Kei-Ichiro Maeda, Hiroko Tsukamura, Yoshihisa Uenoyama
    • Journal Title

      J Reprod Dev.

      Volume: in press Issue: 4 Pages: 359-367

    • DOI

      10.1262/jrd.2020-026

    • NAID

      130007888736

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inducible Kiss1 knockdown in the hypothalamic arcuate nucleus suppressed pulsatile secretion of luteinizing hormone in male mice2020

    • Author(s)
      Shiori Minabe, Sho Nakamura, Eri Fukushima, Marimo Sato, Kana Ikegami, Teppei Goto, Makoto Sanbo, Masumi Hirabayashi, Junko Tomikawa, Takuya Imamura, Naoko Inoue, Yoshihisa Uenoyama, Hiroko Tsukamura, Kei-Ichiro Maeda, Fuko Matsuda
    • Journal Title

      Journal of Reproduction and Development

      Volume: Epub Issue: 4 Pages: 369-375

    • DOI

      10.1262/jrd.2019-164

    • NAID

      130007888724

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Exploring trophoblast-specific Tead4 enhancers through chromatin conformation capture assays followed by functional screening2019

    • Author(s)
      Tomikawa Junko、Takada Shuji、Okamura Kohji、Terao Miho、Ogata-Kawata Hiroko、Akutsu Hidenori、Tanaka Satoshi、Hata Kenichiro、Nakabayashi Kazuhiko
    • Journal Title

      Nucleic Acids Research

      Volume: 48 Issue: 1 Pages: 278-289

    • DOI

      10.1093/nar/gkz1034

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CTCF deletion syndrome: Clinical features and epigenetic delineation2017

    • Author(s)
      Hori I, Kawamura R, Nakabayashi K, Watanabe H, Higashimoto K, Tomikawa J, Ieda D, Ohashi K, Negishi Y, Hattori A, Sugio Y, Wakui K, Hata K, Soejima H, Kurosawa K, Saitoh S
    • Journal Title

      Journal of Medical Genetics

      Volume: 54 Issue: 12 Pages: 836-842

    • DOI

      10.1136/jmedgenet-2017-104854

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 染色体間相互作用を介した細胞系列特異的Tead4発現制御2019

    • Author(s)
      冨川順子、高田修治、岡村浩司、阿久津英憲、田中智、秦健一郎、中林一彦
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 発生段階特異的な機能的ゲノム高次構造の探索2018

    • Author(s)
      冨川順子、西園啓文、秦健一郎、中林一彦
    • Organizer
      第12回日本エピジェネティクス研究会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] Tead4 interactome organized for mouse extraembryonic cell lineage specification2017

    • Author(s)
      Junko Tomikawa, Shuji Takada, Kohji Okamura, Keiko Hayashi, Miho Terao, Hidenori Akutsu, Satoshi Tanaka, Kenichiro Hata, Kazuhiko Nakabayashi
    • Organizer
      72nd Fujihara Seminar
    • Related Report
      2017 Research-status Report
  • [Presentation] 染色体間相互作用を介した細胞系列特異的Tead4発現制御2017

    • Author(s)
      冨川順子、高田修治、岡村浩司、阿久津英憲、田中智、秦健一郎、中林一彦
    • Organizer
      第35回染色体ワークショップ・第16回核ダイナミクス研究会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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