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Dissecting transcription factors using proximity labeling analyses

Research Project

Project/Area Number 19K22607
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 52:General internal medicine and related fields
Research InstitutionNational Center for Child Health and Development

Principal Investigator

Narumi Satoshi  国立研究開発法人国立成育医療研究センター, 分子内分泌研究部, 室長 (40365317)

Project Period (FY) 2019-06-28 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2020: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2019: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Keywords転写 / 転写制御 / プロキシミティラベリング / 転写因子 / 変異 / 転写複合体 / 近接性ラベリング / タンパク質相互作用 / 近接性標識 / 複合体 / オミックス
Outline of Research at the Start

転写複合体は遺伝子機能を調節する役割を持つが、機能のオンとオフを柔軟に行うため、複合体の結合そのものが柔軟であると考えられる。このため、安定的結合を前提とした従来の解析手法では解析が不十分であった。本研究はこのような「ゆるやかな転写複合体」を分析するための新技術プロキシミティ・ラベリング法(近接性標識法)による転写複合体解析を試みるものである。

Outline of Final Research Achievements

Transcriptional regulation is a molecular mechanism that controls the turning on and off of gene functions, but understanding of which molecules are involved in this regulation is lacking. In this study, we employed proximity labeling analysis, a new technique to discover molecular interactions, to analyze transcription factors involved in congenital diseases. As a result, we detected several previously unknown interactions in addition to the previously known ones. This study demonstrates the broad applicability of proximity labeling analysis in the study of transcriptional regulatory mechanisms.

Academic Significance and Societal Importance of the Research Achievements

本研究は転写制御機構研究におけるプロキシミティラベリング法の応用可能性の広さを示すと同時に、本研究の独自性である「野生型分子と変異型分子を比較解析」が転写制御機構研究の有用な切り口になることを示した。現在普及している「転写促進複合体」「転写抑制複合体」という二項対立モデルは適切ではなく、実際には両者が柔軟・可塑的に使い分けられている可能性があり、今後のこの研究分野における研究の方向性を示す成果と言える。

Report

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

    (9 results)

All 2021 2020 2019

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (4 results) (of which Invited: 1 results)

  • [Journal Article] Inactivation of a Frameshift TSH Receptor Variant Val711Phefs*18 is Due to Acquisition of a Hydrophobic Degron.2021

    • Author(s)
      Sugisawa C, Ono M, Kashimada K, Hasegawa T, Narumi S.
    • Journal Title

      J Clin Endocrinol Metab.

      Volume: 106 Issue: 1 Pages: e265-e272

    • DOI

      10.1210/clinem/dgaa772

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Congenital Hypothyroidism Due to Truncating PAX8 Mutations: A Case Series and Molecular Function Studies2020

    • Author(s)
      Iwahashi-Odano Megumi、Nagasaki Keisuke、Fukami Maki、Nishioka Junko、Yatsuga Shuichi、Asakura Yumi、Adachi Masanori、Muroya Koji、Hasegawa Tomonobu、Narumi Satoshi
    • Journal Title

      The Journal of Clinical Endocrinology & Metabolism

      Volume: 105 Issue: 11 Pages: 4055-4065

    • DOI

      10.1210/clinem/dgaa584

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Novel Homozygous Mutation of Thyroid Peroxidase Gene Abolishes a Disulfide Bond Leading to Congenital Hypothyroidism2020

    • Author(s)
      Yakou Fumiyoshi、Suwanai Hirotsugu、Ishikawa Takuya、Itou Mariko、Shikuma Jumpei、Miwa Takashi、Sakai Hiroyuki、Kanekura Kohsuke、Narumi Satoshi、Suzuki Ryo、Odawara Masato
    • Journal Title

      International Journal of Endocrinology

      Volume: 2020 Pages: 1-8

    • DOI

      10.1155/2020/9132372

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification and functional characterization of a novel <i>PAX8</i> mutation (p.His39Pro) causing familial thyroid hypoplasia2020

    • Author(s)
      Iwahashi-Odano M, Fujisawa Y, Ogata T, Nakashima S, Muramatsu M, Narumi S.
    • Journal Title

      Clinical Pediatric Endocrinology

      Volume: 29 Issue: 4 Pages: 173-178

    • DOI

      10.1297/cpe.29.173

    • NAID

      130007922180

    • ISSN
      0918-5739, 1347-7358
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genetics of Congenital Isolated TSH Deficiency: Mutation Screening of the Known Causative Genes and a Literature Review.2019

    • Author(s)
      Sugisawa C, Takamizawa T, Abe K, Hasegawa T, Shiga K, Sugawara H, Ohsugi K, Muroya K, Asakura Y, Adachi M, Daitsu T, Numakura C, Koike A, Tsubaki J, Kitsuda K, Matsuura N, Taniyama M, Ishii S, Satoh T, Yamada M, Narumi S.
    • Journal Title

      J Clin Endocrinol Metab.

      Volume: 104 Issue: 12 Pages: 6229-6237

    • DOI

      10.1210/jc.2019-00657

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] TurboIDによるPAX8近接タンパク質の網羅的解析2021

    • Author(s)
      中尾佳奈子、小田野めぐみ、秋葉和壽、 鳴海覚志
    • Organizer
      第94回 日本内分泌学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 新規ルシフェラーゼ相補アッセイNanoBiTテクノロジーによるPAX8-NKX2-1結合定量系の 開発と臨床応用2021

    • Author(s)
      小田野めぐみ、鳴海覚志
    • Organizer
      第94回 日本内分泌学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 新世代技術によるタンパク質相互作用解析2021

    • Author(s)
      鳴海覚志
    • Organizer
      第94回 日本内分泌学会学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] TurboIDによるPAX8近接タンパク質の網羅的解析2020

    • Author(s)
      中尾佳奈子、小田野めぐみ、秋葉和壽、 鳴海覚志
    • Organizer
      第63回 日本甲状腺学会学術集会
    • Related Report
      2020 Annual Research Report

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Published: 2019-07-04   Modified: 2022-01-27  

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