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Elucidation of complex gene expression regulation dynamics through higher-order genome structure

Research Project

Project/Area Number 19K06612
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 43050:Genome biology-related
Research InstitutionHiroshima University

Principal Investigator

Ochiai Hiroshi  広島大学, 統合生命科学研究科(理), 准教授 (60640753)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsゲノム構造 / 遺伝子発現 / 多能性幹細胞 / 転写 / ライブイメージング
Outline of Research at the Start

マウスES細胞において多能性維持に重要なNanog遺伝子は相互作用するゲノム領域が多数且つ広範囲に散在する、極めて特異な性質を有している。本研究では、マウスES細胞におけるNanogの転写活性化と相互作用領域との関係性を明らかにするために、CRISPRライブラリを用いてNanogの転写調節に関わるゲノム領域を同定し、さらにsequential-FISHおよび独自に確立した特定遺伝子の核内局在および転写活性の可視化技術の改良法によって、高次ゲノム構造動態と遺伝子発現制御の関係理解を目指す。

Outline of Final Research Achievements

In this study, we aimed to elucidate the mechanism of transcriptional regulation by Nanog genes and their interacting regions in mouse ES cells by using sequential-DNA-RNA-FISH and a STREAMING-tag system for visualizing the nuclear localization and transcriptional activity of specific endogenous genes. We developed the STREAMING-tag system and found that RPB1 and BRD4 cluster in the vicinity of Nanog genes only when the gene is in a transcriptionally active state, and published a paper on a preprint server (Ohishi et al., bioRxiv, 2022).

Academic Significance and Societal Importance of the Research Achievements

本研究では、独自に開発した遺伝子イメージング技術を利用して、遺伝子活性状態依存的に特定因子が遺伝子近傍でクラスターを形成することを見出した。本成果は遺伝子発現動態がどのように制御されているかを解く鍵となりえる成果である。遺伝子発現制御機構はあらゆる生命現象に関わる基本的なプロセスであり、大きな学術的意義があるといえる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (28 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (6 results) Journal Article (9 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 8 results,  Open Access: 9 results) Presentation (8 results) (of which Int'l Joint Research: 6 results,  Invited: 6 results) Remarks (5 results)

  • [Int'l Joint Research] Memorial Sloan Kettering Cancer Center/SBP Medical Discovery Institute/Howard Hughes Medical Institute(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Centenary Institute(オーストラリア)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Memorial Sloan Kettering Cancer Center/SBP Medical Discovery Institute/Howard Hughes Medical Institute(米国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Centenary Institute(オーストラリア)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Memorial Sloan Kettering Cancer Center,/SBP Medical Discovery Institute/Howard Hughes Medical Institute(米国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] Centenary Institute(オーストラリア)

    • Related Report
      2019 Research-status Report
  • [Journal Article] iPSC reprogramming-mediated aneuploidy correction in autosomal trisomy syndromes2022

    • Author(s)
      Akutsu Silvia Natsuko、Miyamoto Tatsuo、Oba Daiju、Tomioka Keita、Ochiai Hiroshi、Ohashi Hirofumi、Matsuura Shinya
    • Journal Title

      PLOS ONE

      Volume: 17 Issue: 3 Pages: 1-20

    • DOI

      10.1371/journal.pone.0264965

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ribosomal protein L5 facilitates rDNA-bundled condensate and nucleolar assembly2022

    • Author(s)
      Matsumori Haruka、Watanabe Kenji、Tachiwana Hiroaki、Fujita Tomoko、Ito Yuma、Tokunaga Makio、Sakata-Sogawa Kumiko、Osakada Hiroko、Haraguchi Tokuko、Awazu Akinori、Ochiai Hiroshi、Sakata Yuka、Ochiai Koji、Toki Tsutomu、Ito Etsuro、Goldberg Ilya G、Tokunaga Kazuaki、Nakao Mitsuyoshi、Saitoh Noriko
    • Journal Title

      Life Science Alliance

      Volume: 5 Issue: 7 Pages: 1-18

    • DOI

      10.26508/lsa.202101045

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] STREAMING-tag system reveals spatiotemporal relationships between transcriptional regulatory factors and transcriptional activity2022

    • Author(s)
      Ohishi Hiroaki、Shimada Seiru、Uchino Satoshi、Li Jieru、Sato Yuko、Shintani Manabu、Owada Hitoshi、Ohkawa Yasuyuki、Pertsinidis Alexandros、Yamamoto Takashi、Kimura Hiroshi、Ochiai Hiroshi
    • Journal Title

      bioRxiv

      Volume: -

    • DOI

      10.1101/2022.01.06.472721

    • Related Report
      2021 Annual Research Report
    • Open Access
  • [Journal Article] Single-gene imaging links genome topology, promoter?enhancer communication and transcription control2020

    • Author(s)
      Li Jieru、Hsu Angela、Hua Yujing、Wang Guanshi、Cheng Lingling、Ochiai Hiroshi、Yamamoto Takashi、Pertsinidis Alexandros
    • Journal Title

      Nature Structural & Molecular Biology

      Volume: 27 Issue: 11 Pages: 1032-1040

    • DOI

      10.1038/s41594-020-0493-6

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Genome-wide kinetic properties of transcriptional bursting in mouse embryonic stem cells2020

    • Author(s)
      Ochiai Hiroshi、Hayashi Tetsutaro、Umeda Mana、Yoshimura Mika、Harada Akihito、Shimizu Yukiko、Nakano Kenta、Saitoh Noriko、Liu Zhe、Yamamoto Takashi、Okamura Tadashi、Ohkawa Yasuyuki、Kimura Hiroshi、Nikaido Itoshi
    • Journal Title

      Science Advances

      Volume: 6 Issue: 25

    • DOI

      10.1126/sciadv.aaz6699

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Insufficiency of ciliary cholesterol in hereditary Zellweger syndrome.2020

    • Author(s)
      Miyamoto T, Hosoba K, Itabashi T, Iwane AH, Akutsu AN, Ochiai H, Saito Y, Yamamoto T, Matsuura S
    • Journal Title

      EMBO Journal

      Volume: - Issue: 12

    • DOI

      10.15252/embj.2019103499

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] PHi-C: deciphering Hi-C data into polymer dynamics2020

    • Author(s)
      Shinkai Soya、Nakagawa Masaki、Sugawara Takeshi、Togashi Yuichi、Ochiai Hiroshi、Nakato Ryuichiro、Taniguchi Yuichi、Onami Shuichi
    • Journal Title

      NAR Genomics and Bioinformatics

      Volume: 2 Issue: 2

    • DOI

      10.1093/nargab/lqaa020

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of dynamic nuclear deformation on genomic architecture reorganization2019

    • Author(s)
      Seirin-Lee Sungrim、Osakada Fumitaka、Takeda Junichi、Tashiro Satoshi、Kobayashi Ryo、Yamamoto Takashi、Ochiai Hiroshi
    • Journal Title

      PLOS Computational Biology

      Volume: 15 Issue: 9 Pages: 1-25

    • DOI

      10.1371/journal.pcbi.1007289

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Single-Molecule Nanoscopy Elucidates RNA Polymerase II Transcription at Single Genes in Live Cells2019

    • Author(s)
      Li Jieru、Dong Ankun、Saydaminova Kamola、Chang Hill、Wang Guanshi、Ochiai Hiroshi、Yamamoto Takashi、Pertsinidis Alexandros
    • Journal Title

      Cell

      Volume: 178 Issue: 2 Pages: 491-506

    • DOI

      10.1016/j.cell.2019.05.029

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] STREAMING-tag system: A novel technology to analyze the spatiotemporal relationship between transcriptional regulators and transcriptional dynamics at the single gene level2022

    • Author(s)
      Hiroshi Ochiai
    • Organizer
      The 30th Hot Spring Harbor International Symposium -Chromatin Potential in Development and Differentiation
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Genome-wide kinetic properties of transcriptional bursting revealed by single cell analysis2021

    • Author(s)
      Hiroshi Ochiai
    • Organizer
      The 2nd ASHBi SignAC Workshop, Integrating Single-cell Analysis and Mathematics
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Single-gene imaging reveals the relationship between the transcriptional activity of single genes and the formation of transcriptional regulatory factor clusters2021

    • Author(s)
      Hiroaki Ohishi, Seiru Shimada, Satoshi Uchino, Li Jieru, Yuko Sato, Alexandros Pertsinidis, Takashi Yamamoto, Hiroshi Kimura, Hiroshi Ochiai
    • Organizer
      Cold Spring Harbor Laboratory Meeting, Mechanisms of Eukaryotic Transcription
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] クロマチン潜在能による転写バースト制御2020

    • Author(s)
      Hiroshi Ochiai
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 分子の動きを「見る」ためのゲノム編集技術2020

    • Author(s)
      落合 博
    • Organizer
      第4回 広島大学先端科学セミナー「“ゲノム編集”で未来社会を拓く」
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Transcriptional bursting induces gene expression heterogeneity in mES cells2019

    • Author(s)
      Hiroshi Ochiai
    • Organizer
      Chromosome Dynamics 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Transcriptional bursting induces gene expression heterogeneity in mouse embryonic stem cells2019

    • Author(s)
      Hiroshi Ochiai
    • Organizer
      Single Molecule Imaging of Chromatin Symposium
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] CRISPR ライブラリスクリーニングによる転写バースト関連遺伝子の探索2019

    • Author(s)
      落合博、 山本卓
    • Organizer
      日本ゲノム編集学会 第4回大会
    • Related Report
      2019 Research-status Report
  • [Remarks] 広島大学・統合生命・分子遺伝・落合グループ

    • URL

      https://home.hiroshima-u.ac.jp/ochiai/

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
  • [Remarks] researchmap

    • URL

      https://researchmap.jp/HiroshiOchiai/

    • Related Report
      2021 Annual Research Report 2020 Research-status Report 2019 Research-status Report
  • [Remarks] researchgate

    • URL

      https://www.researchgate.net/profile/Hiroshi-Ochiai-2

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
  • [Remarks] 広島大学 大学院 統合生命科学研究科 分子遺伝学研究室 落合グループ

    • URL

      https://home.hiroshima-u.ac.jp/ochiai/index_jp.html

    • Related Report
      2019 Research-status Report
  • [Remarks] researchgate

    • URL

      https://www.researchgate.net/profile/Hiroshi_Ochiai3/?ev=hdr_xprf

    • Related Report
      2019 Research-status Report

URL: 

Published: 2019-04-18   Modified: 2023-01-30  

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