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Comprehensive elucidation of multifactorial interactions that establish the transcription unity mechanism

Planned Research

Project AreaElucidation of the mechanisms of transcriptional unity by understanding spatiotemporal multifactorial interactions
Project/Area Number 21H05159
Research Category

Grant-in-Aid for Transformative Research Areas (B)

Allocation TypeSingle-year Grants
Review Section Transformative Research Areas, Section (III)
Research InstitutionYokohama City University

Principal Investigator

TAKAHASHI Hidehisa  横浜市立大学, 医学研究科, 教授 (30423544)

Co-Investigator(Kenkyū-buntansha) 西山 晃  横浜市立大学, 医学部, 准教授 (80589664)
Project Period (FY) 2021-08-23 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥54,600,000 (Direct Cost: ¥42,000,000、Indirect Cost: ¥12,600,000)
Fiscal Year 2023: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2022: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2021: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Keywords遺伝子発現 / 転写 / RNAポリメラーゼII / メディエーター複合体 / 液ー液相分離 / 転写制御 / IRF8
Outline of Research at the Start

これまでの遺伝子発現制御の研究においては、核内で一連の転写のプロセスが連続反応によって進行し、RNAが合成されると考えられてきた。ところが、最近の研究によって、「転写プロセス全体が密な相互連携によって一体化(Unity: ユニティー)し、遺伝子発現を制御する機構」(転写ユニティー機構)の存在が強く示唆された。そこで本研究では、転写ユニティー機構を構築する多因子間相互作用の解明を目指す。

Outline of Final Research Achievements

Our recent studies have suggested that transcription regulation is difficult to understand only by conventional models and that there is a mechanism in which the entire transcription process is unified by multifactorial interactions and regulates gene expression, which we called transcriptional unity mechanism. In this study, we focus on the Mediator complexes that are suggested to play an important role in the multifactor interactions in the transcription unity mechanism, and elucidate the roles of these factors in this mechanism, and clarify the molecular mechanism of the transcription unity.

Academic Significance and Societal Importance of the Research Achievements

本研究は従来の転写研究では着目されてこなかった視点に基づいて転写制御機構を解明するものであり、学術的独自性が高く、未知の転写制御機構が解明されることが強く期待できる。また、最新の知見から、多因子間相互作用による転写ユニティー機構は、DNA修復や複製、細胞周期などの他の核内機能においても機能していることが考えられ、本研究の推進は転写研究と他の核内機能の研究を融合させた新たな研究分野の創造につながることが期待できる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (24 results)

All 2023 2022 2021 Other

All Int'l Joint Research (2 results) Journal Article (13 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 11 results,  Open Access: 11 results) Presentation (6 results) (of which Invited: 3 results) Remarks (3 results)

  • [Int'l Joint Research] ストワーズ医学研究所(米国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Stowers Institute for Medical Research(米国)

    • Related Report
      2021 Annual Research Report
  • [Journal Article] RNA Foci in Two bi‐Allelic RFC1 Expansion Carriers2023

    • Author(s)
      Wada Taishi、Doi Hiroshi, et al.
    • Journal Title

      Annals of Neurology

      Volume: 95 Issue: 3 Pages: 607-613

    • DOI

      10.1002/ana.26848

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sez6l2 autoimmunity in a large cohort study2023

    • Author(s)
      Abe M, Yaguchi H, Kudo A, Nagai A, Shirai S, Takahashi-Iwata I, Matsushima M, Nakamura N, Isahaya K, Yamano Y, Ashida S, Kasai T, Tanaka K, Watanabe M, Kondo T, Takahashi H, Hatakeyama S, Takekoshi A, Kimura A, Shimohata T, Yabe I.
    • Journal Title

      Journal of Neurology, Neurosurgery & Psychiatry

      Volume: 94 Issue: 8 Pages: 667-668

    • DOI

      10.1136/jnnp-2022-330194

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MED26‐containing Mediator may orchestrate multiple transcription processes through organization of nuclear bodies2023

    • Author(s)
      Suzuki Hidefumi、Furugori Kazuki、Abe Ryota、Ogawa Shintaro、Ito Sayaka、Akiyama Tomohiko、Horiuchi Keiko、Takahashi Hidehisa
    • Journal Title

      BioEssays

      Volume: 45 Issue: 4

    • DOI

      10.1002/bies.202200178

    • Related Report
      2023 Annual Research Report 2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation and Utilization of a Monoclonal Antibody against Hepatitis B Virus Core Protein for a Comprehensive Interactome Analysis2022

    • Author(s)
      Nakai Yusuke、Miyakawa Kei、Yamaoka Yutaro、Hatayama Yasuyoshi、Nishi Mayuko、Suzuki Hidefumi、Kimura Hirokazu、Takahashi Hidehisa、Kimura Yayoi、Ryo Akihide
    • Journal Title

      Microorganisms

      Volume: 10 Issue: 12 Pages: 2381-2381

    • DOI

      10.3390/microorganisms10122381

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Angiotensin II type-1 receptor-associated protein interacts with transferrin receptor-1 and promotes its internalization2022

    • Author(s)
      Abe Eriko、Yamashita Akio、Hirota Keigo、Yamaji Takahiro、Azushima Kengo、Urate Shingo、Suzuki Toru、Tanaka Shohei、Taguchi Shinya、Tsukamoto Shunichiro、Uehara Tatsuki、Wakui Hiromichi、Tamura Kouichi、Takahashi Hidehisa
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 17376-17376

    • DOI

      10.1038/s41598-022-22343-5

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PAR3 restricts the expansion of neural precursor cells by regulating hedgehog signaling2022

    • Author(s)
      Hirose T, Sugitani Y, Kurihara H, Kazama H, Kusaka C, Noda T, Takahashi H, Ohno S.
    • Journal Title

      Development.

      Volume: 149 Issue: 21

    • DOI

      10.1242/dev.199931

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dual function of SF3B2 on chromatin and RNA to regulate transcription in head and neck squamous cell carcinoma2022

    • Author(s)
      Kitamura Koji、Suzuki Hidefumi、Abe Ryota、Inohara Hidenori、Kaneda Yasufumi、Takahashi Hidehisa、Nimura Keisuke
    • Journal Title

      Cell & Bioscience

      Volume: 12 Issue: 1 Pages: 92-92

    • DOI

      10.1186/s13578-022-00812-8

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The 3′ Pol II pausing at replication-dependent histone genes is regulated by Mediator through Cajal bodies’ association with histone locus bodies2022

    • Author(s)
      Suzuki Hidefumi、Abe Ryota、Shimada Miho、Hirose Tomonori、Hirose Hiroko、Noguchi Keisuke、Ike Yoko、Yasui Nanami、Furugori Kazuki、Yamaguchi Yuki、Toyoda Atsushi、Suzuki Yutaka、Yamamoto Tatsuro、Saitoh Noriko、Sato Shigeo、Tomomori-Sato Chieri、Conaway Ronald C.、Conaway Joan W.、Takahashi Hidehisa
    • Journal Title

      Nature Communications

      Volume: 13 Issue: 1 Pages: 2905-2905

    • DOI

      10.1038/s41467-022-30632-w

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pol Ⅱ動態の新常識―ポージングによる新たな転写制御機構2022

    • Author(s)
      高橋秀尚
    • Journal Title

      実験医学増刊

      Volume: 40(12) Pages: 1910-1917

    • Related Report
      2022 Annual Research Report
  • [Journal Article] The nuclear transcription factor, TAF7, is a cytoplasmic regulator of protein synthesis2021

    • Author(s)
      Cheng Dan、Semmens Kevin、McManus Elizabeth、Chen Qingrong、Meerzaman Daoud、Wang Xiantao、Hafner Markus、Lewis Brian A.、Takahashi Hidehisa、Devaiah Ballachanda N.、Gegonne Anne、Singer Dinah S.
    • Journal Title

      Science Advances

      Volume: 7 Issue: 50

    • DOI

      10.1126/sciadv.abi5751

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] <i>De novo ARF3</i> variants cause neurodevelopmental disorder with brain abnormality2021

    • Author(s)
      Sakamoto M、Sasaki K、Sugie A、Nitta Y、Kimura T、G?rsoy S、Cinleti T、Iai M、Sengoku T、Ogata K、Suzuki A、Okamoto N、Iwama K、Tsuchida N、Uchiyama Y、Koshimizu E、Fujita A、Hamanaka K、Miyatake S、Mizuguchi T、Taguri M、Ito S、Takahashi H、Miyake N、Matsumoto N
    • Journal Title

      Human Molecular Genetics

      Volume: 31 Issue: 1 Pages: 69-81

    • DOI

      10.1093/hmg/ddab224

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] De novo ATP1A3 variants cause polymicrogyria2021

    • Author(s)
      Miyatake Satoko、Kato Mitsuhiro、Kumamoto Takuma、Hirose Tomonori、他
    • Journal Title

      Science Advances

      Volume: 7 Issue: 13 Pages: 2368-2368

    • DOI

      10.1126/sciadv.abd2368

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] メディエーター複合体のコンポーネントMED26による新たな転写制御機構2021

    • Author(s)
      鈴木秀文,高橋秀尚
    • Journal Title

      Seikagaku

      Volume: 93(6) Pages: 810-814

    • NAID

      40022783946

    • Related Report
      2021 Annual Research Report
  • [Presentation] HPV-18産生RNAによるがん原遺伝子の転写活性化機構の解明2023

    • Author(s)
      古郡華月, 鈴木秀文, 阿部竜太, 高橋秀尚
    • Organizer
      日本プロテオーム学会2023年大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] HPV-18産生RNAをコアとした液滴形成によるがん原遺伝子の転写活性化機構2023

    • Author(s)
      古郡華月, 鈴木秀文, 阿部竜太, 高橋秀尚
    • Organizer
      第96回日本生化学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] メディエーター複合体の液滴による転写ユニティー制御機構の解明2023

    • Author(s)
      鈴木秀文, 阿部竜太, 池 陽子, 古郡華月, 小川真太郎, 豊田敦, 鈴木穣, 井野洋子, 木村弥生, 秋山智彦, 石川博子, 廣瀬智威, 山本達郎, 斉藤典子, 山口雄輝, 高橋秀尚
    • Organizer
      第96回日本生化学会大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] LEC構成因子ZC3H8によるsnRNA遺伝子の発現制御機構の解明2023

    • Author(s)
      野口慶介, 鬼澤理紗, 阿部竜太, 仙石 徹, 緒方一博, 池 陽子, 井野洋子, 木村弥生, 鈴木秀文, 髙橋秀尚
    • Organizer
      第46回日本分子生物学会年会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] HPV-18産生RNAをコアとした液滴形成によるがん原遺伝子の転写活性化機構2023

    • Author(s)
      古郡華月, 鈴木秀文, 阿部竜太, 高橋秀尚
    • Organizer
      第46回日本分子生物学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Poll Ⅱの一時停止および核体凝集体の制御におけるメディエーター複合体の役割.2022

    • Author(s)
      鈴木秀文, 阿部竜太, 嶋田美穂, 廣瀬智威, 廣瀬博子, 野口慶介, 池 陽子, 安井七海, 古郡華月, 山口雄輝, 豊田 敦, 鈴木 穣, 山本達郎, 斉藤典子, Shigeo Sato, Chieri Tomomori-Sato, Ronald C. Conaway, Joan W. Conaway, 高橋秀尚
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Remarks] https://ycu-molecularbiology.jp/

    • Related Report
      2023 Annual Research Report
  • [Remarks] https://ycu-molecularbiology.jp/

    • Related Report
      2022 Annual Research Report
  • [Remarks] 研究室のホームページ

    • URL

      https://ycu-molecularbiology.jp/

    • Related Report
      2021 Annual Research Report

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Published: 2021-10-22   Modified: 2025-01-30  

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