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Neuroepigenetic regulation of gene expression by DNA topooisomesase IIbeta

Research Project

Project/Area Number 18K06349
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 45010:Genetics-related
Research InstitutionOkayama University

Principal Investigator

Miyaji Mary  岡山大学, 医歯薬学総合研究科, 助教 (50349255)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsNerobiology / Epigenetics / Social behavior / Nuclear structure / 神経細胞 / 終末分化 / 核内構造 / 遺伝子発現制御 / 神経特異的遺伝子 / 神経細胞分化 / エピジェネティック / ニューロン
Outline of Final Research Achievements

We established three lines in which mutations were introduced into the topo IIβ gene by genome editing. The topo IIβ homozygous mutants were found to be lethal within a week after hatching. We performed mRNA-seq analyses using heads of homozygous, heterozygous, and wild-type individuals immediately after hatching, and revealed that the expression of many neuron-specific long genes was decreased in the homozygous mutants. Similar decreases were observed in the heterozygotes, though the decrease was lower in the heterozygotes than in the homozygotes. We are trying to discover behavioral abnormalities of heterozygous mutants with a focus on social behaviors.

Academic Significance and Societal Importance of the Research Achievements

本研究では日本オリジナルのモデル脊椎動物であるメダカを用いて遺伝学と行動学的解析を組合せることにより,トポIIβが新規のエピジェネティック制御で神経機能に重要な遺伝子の発現を制御する機構と,その破綻が高次脳機能に及ぼす影響を明らかにすることを目的として行われた.実際,トポIIβが発現誘導する遺伝子が多数同定され,それらに多くの神経・精神疾患の関連遺伝子が含まれていた.今後の行動評価実験によりASDをはじめとする精神神経疾患の病態理解に繋がることが期待される

Report

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

    (5 results)

All 2020 2019 2018

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (4 results)

  • [Journal Article] Topoisomerase IIβ targets DNA crossovers formed between distant homologous sites to induce chromatin opening2020

    • Author(s)
      Miyaji Mary、Furuta Ryohei、Hosoya Osamu、Sano Kuniaki、Hara Norikazu、Kuwano Ryozo、Kang Jiyoung、Tateno Masaru、Tsutsui Kimiko M.、Tsutsui Ken
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1

    • DOI

      10.1038/s41598-020-75004-w

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] トポイソメラーゼIIβは遠隔ゲノム部位の相同配列間に働いてクロマチンを脱凝縮し神経関連遺伝子の発現に関与する2019

    • Author(s)
      宮地まり,古田良平, 細谷 修, 佐野訓明, 筒井公子, 筒井 研
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] トポイソメラーゼIIβの遠隔ゲノム部位間での働きを解析するeTIP-seq法の検証2019

    • Author(s)
      古田良平, 宮地まり, 細谷 修, 佐野訓明, 筒井公子, 筒井 研
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] トポイソメラーゼIIβは神経細胞終末分化において遠隔ゲノム部位の相同配列間に働きクロマチン脱凝縮を誘導する2019

    • Author(s)
      宮地 まり
    • Organizer
      第 36 回 染色体ワークショップ 第 17 回 核ダイナミクス研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] hnRNPU/ SAF-A/ SP120はRNA存在下でMARに選択的に結合する2018

    • Author(s)
      宮地 まり
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report

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

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