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Analysis of transcriptional regulation mechanisms and artificial modification of DNA structure by CRISPR/Cas system.

Research Project

Project/Area Number 18K15045
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 48040:Medical biochemistry-related
Research InstitutionGifu University

Principal Investigator

Sato Katsuya  岐阜大学, 大学院医学系研究科, 助教 (60733508)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsAID / CRISPR/Cas9 / 遺伝子発現制御 / Aicda / 遺伝子転写調節 / 転写調節 / エンハンサー / dCas9
Outline of Final Research Achievements

Activation-induced cytidine deaminase (AID), which encoded by Aicda, is essential for class switch recombination (CSR) and somatic hypermutation (SHM). Although the expression of AID is tightly regulated and restricted in activated B cells, it is thought that aberrant expression of AID can be involved in tumor progression because of its high mutagenetic potential. Many transcription factors have been identified as regulators of Aicda. These factors should coordinately regulate Aicda, but the detailed mechanisms are not fully understood. IRF4, one of the essential factors for AID expression, forms a complex with multiple transcription factors such as PU.1 and Batf. We identified that IRF4-Batf-Jun complex are more important than IRF4-PU.1 complex for AID expression. Also, we tried to analyze 3D structure of Aicda locus by dCas9 fused with transcription activated protein or Luciferase protein. Furthermore, we tried to reconstitute activated Aicda locus by dCas9 system.

Academic Significance and Societal Importance of the Research Achievements

近年、従来着目されてきた転写因子とDNAの単純な相互作用による転写調節に加え、遺伝子座全体の構造や、核内においてDNAの存在する区画によって転写が活発な領域とそうでない領域に分けられるという考え方が受け入れられつつある。しかしながらこれらを知る為には3C法やHi-C法といった煩雑な解析が必要であった。今後改善が必要であるものの、本研究で検討したdCas9を用いることでより簡便に遺伝子座の構造解析を行えるようになると考えられる。また、こうして得られた知見をもとにDNA構造を改変することでAID発現の調節が出来れば、将来的に自己免疫疾患の克服や効率的なワクチン開発といった分野への応用が期待できる。

Report

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

    (13 results)

All 2021 2020 2019 2018

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (10 results)

  • [Journal Article] The interaction between PLEKHG2 and ABL1 suppresses cell growth via the NF-κB signaling pathway in HEK293 cells2019

    • Author(s)
      Nishikawa Masashi、Nakano Shun、Nakao Hiromu、Sato Katsuya、Sugiyama Tsuyoshi、Akao Yukihiro、Nagaoka Hitoshi、Yamakawa Hisashi、Nagase Takahiro、Ueda Hiroshi
    • Journal Title

      Cellular Signalling

      Volume: 61 Pages: 93-107

    • DOI

      10.1016/j.cellsig.2019.04.016

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] DBS is activated by EPHB2/SRC signaling-mediated tyrosine phosphorylation in HEK293 cells2019

    • Author(s)
      Nakano Shun、Nishikawa Masashi、Asaoka Rina、Ishikawa Natsuko、Ohwaki Chisato、Sato Katsuya、Nagaoka Hitoshi、Yamakawa Hisashi、Nagase Takahiro、Ueda Hiroshi
    • Journal Title

      Molecular and Cellular Biochemistry

      Volume: 459 Pages: 83-93

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] The circulating immunoglobulins negatively impact on the parasite clearance in the liver of Leishmania donovani-infected mice via dampening ROS activity2018

    • Author(s)
      Srinontong Piyarat、Wu Zhiliang、Sato Katsuya、Nagaoka Hitoshi、Maekawa Yoichi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 506 Issue: 1 Pages: 20-26

    • DOI

      10.1016/j.bbrc.2018.10.055

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] AP-1ファミリー転写因子Jun-BATFによるAID遺伝子発現調節2021

    • Author(s)
      佐藤克哉、安田一、堀賢一郎、Li Yupeng、長岡仁
    • Organizer
      第84回日本生化学会中部支部例会・シンポジウム
    • Related Report
      2020 Annual Research Report
  • [Presentation] AP-1ファミリー転写因子Jun-BATFおよびIRF4複合体によるAID遺伝子発現調節2021

    • Author(s)
      佐藤克哉、安田一、堀賢一郎、Li Yupeng、長岡仁
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] AP-1ファミリー転写因子Junによる抗体遺伝子改変酵素AIDの発現調節2020

    • Author(s)
      安田 一、佐藤 克哉、杉山 貴紹、金子 朋仁、堀 賢一郎、李 育朋、長岡 仁
    • Organizer
      日本薬学会 第140回年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Regulation of AID expression by transcription factor BATF-IRF complex2019

    • Author(s)
      Katsuya Sato, Hajime Yasuda, Kenichiro Hori, Hitoshi Nagaoka
    • Organizer
      Nagoya Immunology Network in NCU
    • Related Report
      2019 Research-status Report
  • [Presentation] Rho活性化因子PLEKHG2と非受容体チロシンキナーゼABL1の蛋白質間相互作用が誘導するNF-kBシグナルを介した細胞増殖抑制2019

    • Author(s)
      西川将司、中野駿、中尾拡、佐藤克哉、杉山剛志、赤尾幸博、長岡仁、山川央、長瀬隆弘、上田浩
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] AID遺伝子発現調節における転写因子Junの関与2019

    • Author(s)
      佐藤 克哉、杉山貴紹、安田一、堀 賢一郎、李育朋、長岡 仁
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Evaluation of function of transcription factor, Jun, in Aicda gene regulation2019

    • Author(s)
      Katsuya Sato、Hitoshi Nagaoka
    • Organizer
      第48回日本免疫学会総会・学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] AID遺伝子発現調節における転写因子BATFとIRF4の相互作用2018

    • Author(s)
      佐藤克哉、安田一、堀賢一郎、Li Yupeng、長岡仁
    • Organizer
      第82回日本生化学会中部支部例会・シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] 転写因子BATF-IRF4複合体による遺伝子座の高次構造形成とAID遺伝子発現調節2018

    • Author(s)
      佐藤 克哉、堀 賢一郎、安田 一、長岡 仁
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Evaluation of Aicda gene expression by signal factor controlled by BATF2018

    • Author(s)
      Katsuya Sato、Hitoshi Nagaoka
    • Organizer
      第47回日本免疫学会総会・学術集会
    • Related Report
      2018 Research-status Report

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

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