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Comprehensive enhancer analysis and molecular pathogenesis of leukemia using our novel technology

Research Project

Project/Area Number 18H03992
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Murakawa Yasuhiro  国立研究開発法人理化学研究所, 生命医科学研究センター, チームリーダー (50765469)

Co-Investigator(Kenkyū-buntansha) 高折 晃史  京都大学, 医学研究科, 教授 (20324626)
白川 康太郎  京都大学, 医学研究科, 助教 (80728270)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥44,720,000 (Direct Cost: ¥34,400,000、Indirect Cost: ¥10,320,000)
Fiscal Year 2020: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
Fiscal Year 2019: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
Fiscal Year 2018: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Keywords白血病 / エンハンサー / ゲノム解析技術 / バイオマーカー / 転写ネットワーク / NET-CAGE / 造血器悪性腫瘍 / ヒトゲノム科学 / ノンコーディングゲノム・RNA / 次世代シークエンシング / バイオインフォマティクス / ゲノム科学 / 遺伝子発現制御 / 次世代シークエンサー / 造血器腫瘍 / NET-CAGE法 / 腫瘍 / ゲノム解析
Outline of Final Research Achievements

Leukemia is an intractable hematologic tumor that presents with a wide variety of clinical and cellular features. Epigenetic abnormalities are important in leukemia. In particular, transcriptional regulation of genes by enhancers determines the identity of leukemic cells. Activated enhancers can be identified with high resolution by detecting eRNAs synthesized from enhancers by next-generation sequencing. In this project, we developed a novel technology for ultra-sensitive and comprehensive detection of eRNAs and applied it to around 100 hematopoietic malignancy specimens to identify leukemia enhancer transcription programs. By integrating clinical and genomic data, RNA expression information, and epigenetic information, we identified novel therapeutic targets and biomarkers.

Academic Significance and Societal Importance of the Research Achievements

白血病は若年者から高齢者まで幅広い年齢層に発症する難治性の血液の腫瘍である。しかしながら、その分子メカニズムはほとんどわかっていなかった。腫瘍細胞の状態の決定に肝になるエンハンサー(遺伝子の発現スイッチとして働く)を超高感度に同定できる新しいゲノム解析技術を開発した。これにより、白血病細胞の詳細な分子状態の理解につながり、大規模な患者検体を用いた解析により、新しいバイオマーカーや創薬標的の候補を多数取得することに成功した。これにより、白血病の根源的な分子メカニズムの解明のみならず、新規治療法の創出に資する成果をあげることができた。

Report

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

    (20 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (2 results) Journal Article (7 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 7 results,  Open Access: 4 results) Presentation (11 results) (of which Int'l Joint Research: 2 results,  Invited: 11 results)

  • [Int'l Joint Research] カロリンスカ研究所(スウェーデン)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] カロリンスカ研究所(スウェーデン)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] APOBEC3B is preferentially expressed at the G2/M phase of cell cycle2021

    • Author(s)
      Hirabayashi Shigeki、Shirakawa Kotaro、Horisawa Yoshihito、Matsumoto Tadahiko、Matsui Hiroyuki、Yamazaki Hiroyuki、Sarca Anamaria Daniela、Kazuma Yasuhiro、Nomura Ryosuke、Konishi Yoshinobu、Takeuchi Suguru、Stanford Emani、Kawaji Hideya、Murakawa Yasuhiro、Takaori-Kondo Akifumi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 546 Pages: 178-184

    • DOI

      10.1016/j.bbrc.2021.02.008

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Significance of HMGA2 expression as independent poor prognostic marker in perihilar and distal cholangiocarcinoma resected with curative intent2021

    • Author(s)
      Takahashi Tomoaki、Kawaji Hideya、Murakawa Yasuhiro、Hayashizaki Yoshihide、Murakami Takashi、Yabushita Yasuhiro、Homma Yuki、Kumamoto Takafumi、Matsuyama Ryusei、Endo Itaru
    • Journal Title

      European Journal of Surgical Oncology

      Volume: 47 Issue: 2 Pages: 394-400

    • DOI

      10.1016/j.ejso.2020.08.005

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CAGE-seq analysis of osteoblast derived from cleidocranial dysplasia human induced pluripotent stem cells2020

    • Author(s)
      Ooki Akio、Onodera Shoko、Saito Akiko、Oguchi Akiko、Murakawa Yasuhiro、Sakamoto Teruo、Sueishi Kenji、Nishii Yasushi、Azuma Toshifumi
    • Journal Title

      Bone

      Volume: 141 Pages: 115582-115582

    • DOI

      10.1016/j.bone.2020.115582

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] NET-CAGE characterizes the dynamics and topology of human transcribed cis-regulatory elements2019

    • Author(s)
      Hirabayashi Shigeki、Bhagat Shruti、Matsuki Yu、Takegami Yujiro、Uehata Takuya、Kanemaru Ai、Itoh Masayoshi、Shirakawa Kotaro、Takaori-Kondo Akifumi、Takeuchi Osamu、Carninci Piero、Katayama Shintaro、Hayashizaki Yoshihide、Kere Juha、Kawaji Hideya、Murakawa Yasuhiro
    • Journal Title

      Nature Genetics

      Volume: 51 Issue: 9 Pages: 1369-1379

    • DOI

      10.1038/s41588-019-0485-9

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] HTLV-1 contains a high CG dinucleotide content and is susceptible to the host antiviral protein ZAP2019

    • Author(s)
      Miyazato Paola、Matsuo Misaki、Tan Benjy J. Y.、Tokunaga Michiyo、Katsuya Hiroo、Islam Saiful、Ito Jumpei、Murakawa Yasuhiro、Satou Yorifumi
    • Journal Title

      Retrovirology

      Volume: 16 Issue: 1 Pages: 38-38

    • DOI

      10.1186/s12977-019-0500-3

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Codon bias confers stability to human mRNAs2019

    • Author(s)
      Hia Fabian、Yang Sheng Fan、Shichino Yuichi、Yoshinaga Masanori、Murakawa Yasuhiro、Vandenbon Alexis、Fukao Akira、Fujiwara Toshinobu、Landthaler Markus、Natsume Tohru、Adachi Shungo、Iwasaki Shintaro、Takeuchi Osamu
    • Journal Title

      EMBO reports

      Volume: 20 Issue: 11

    • DOI

      10.15252/embr.201948220

    • NAID

      120006767912

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Selective Activation of Alternative MYC Core Promoters by Wnt-Responsive Enhancers2018

    • Author(s)
      Bardales Jorge、Wieser Evin、Kawaji Hideya、Murakawa Yasuhiro、Darzacq Xavier
    • Journal Title

      Genes

      Volume: 9 Issue: 6 Pages: 270-270

    • DOI

      10.3390/genes9060270

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] A new genomic and computational approach to study human genomic enhancers and its association with diseases2021

    • Author(s)
      村川泰裕
    • Organizer
      1st International Symposium of CCII
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Identification of Transcriptional Regulators Using Novel Next-generation Sequencing Technology2021

    • Author(s)
      村川泰裕
    • Organizer
      85th Annual Scientific Meeting of the Japanese Circulation Society
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Decoding functional DNA elements in the human genome2021

    • Author(s)
      村川泰裕
    • Organizer
      1st ASHBi SignAC Workshop
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] RNAの生死から俯瞰する遺伝子発現制御2021

    • Author(s)
      村川泰裕
    • Organizer
      IPR Seminar
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Novel NET-CAGE Technology Reveals the Dynamics and Topology of Human Cis-regulatory Elements2019

    • Author(s)
      村川泰裕
    • Organizer
      Asia Pacific Conference on Human Genetics 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 腎組織のイメージングビッグデータ解析2019

    • Author(s)
      村川泰裕
    • Organizer
      第5回腎と生活習慣病先端医学セミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 腎組織のイメージングビッグデータ解析2018

    • Author(s)
      1.村川泰裕、久米慧嗣、前田光代、須賀三雄、田村勝、小林紀郎
    • Organizer
      第61回日本腎臓学会学術総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 新規のNET-CAGE-seq法により明らかになる遺伝子発現ネットワークの正体2018

    • Author(s)
      村川泰裕
    • Organizer
      第91回日本内分泌学会学術総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ゲノムデータの再生医療への応用 iPS細胞におけるゲノム変異の解明2018

    • Author(s)
      村川泰裕
    • Organizer
      第17回日本再生医療学会総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] NET-CAGEの現状と展望2018

    • Author(s)
      村川泰裕
    • Organizer
      第6回理研・順天堂共同研究発表会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 次世代ヒト科学を推進するゲノム基盤の構築2018

    • Author(s)
      村川泰裕 廣瀬直毅 佐野浩美 川路英哉 河合純
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
    • Invited

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

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