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Epigenetics analysis of HTLV-1 provirus for pathogenesis of ATL

Research Project

Project/Area Number 16K19580
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Hematology
Research InstitutionKumamoto University

Principal Investigator

Katsuya Hiroo  熊本大学, エイズ学研究センター, 特任助教 (80632041)

Co-Investigator(Renkei-kenkyūsha) SATOU Yorifumi  熊本大学, エイズ学研究センター, 教授 (70402807)
Research Collaborator MIYAZATO Paola  熊本大学, 国際先端医学研究機構, 特任助教 (90573105)
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsHTLV-1 / 成人T細胞白血病-リンパ腫 / エンハンサー / ChIP-seq / 転写因子 / 内科 / ウイルス
Outline of Final Research Achievements

The nucleosome-free region (NFR) was found near the 3’LTR of HTV-1 provirus by MNase-sequence in both an ATL cell line and PBMCs from the ATL patients. Chromatin immunoprecipitation sequencing (ChIP-seq) showed the histone modification pattern of enhancer regions in the NFR, such as H3K4me1, H3K4me2, and H3K27Ac. The enhancer function of the NFR was also confirmed by Luciferase Reporter Assay. Furthermore, the binding of transcriptional factors, SRF and ELK-1, was detectable in the NFR by ChIP-seq and electrophoretic mobility shift assay. These data suggests that the NFR in HTLV-1 provirus plays a role of enhancer for HBZ expression, which is reverse-transcribed from 3’LTR, and might contribute to persistent infection in infected individuals.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (22 results)

All 2017 2016 Other

All Int'l Joint Research (2 results) Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 6 results,  Acknowledgement Compliant: 3 results) Presentation (13 results) (of which Int'l Joint Research: 4 results)

  • [Int'l Joint Research] インペリアル大学免疫学(英国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] インペリアル大学(英国)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Dynamics and mechanisms of clonal expansion of HIV-1-infected cells in a humanized mouse model2017

    • Author(s)
      Satou Yorifumi、Katsuya Hiroo、Fukuda Asami、Misawa Naoko、Ito Jumpei、Uchiyama Yoshikazu、Miyazato Paola、Islam Saiful、Fassati Ariberto、Melamed Anat、Bangham Charles R. M.、Koyanagi Yoshio、Sato Kei
    • Journal Title

      Scientific Reports

      Volume: 7(1) Issue: 1 Pages: 6913-6913

    • DOI

      10.1038/s41598-017-07307-4

    • NAID

      120006364095

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Treatment advances and prognosis for patients with adult T-cell leukemia-lymphoma2017

    • Author(s)
      Katsuya Hiroo、Ishitsuka Kenji
    • Journal Title

      Journal of Clinical and Experimental Hematopathology

      Volume: 57 Issue: 3 Pages: 87-97

    • DOI

      10.3960/jslrt.17008

    • NAID

      130006286271

    • ISSN
      1346-4280, 1880-9952
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prognostic index for chronic- and smoldering-type adult T-cell leukemia-lymphoma2017

    • Author(s)
      Katsuya Hiroo、Shimokawa Mototsugu、Ishitsuka Kenji、Kawai Kazuhiro、Amano Masahiro、Utsunomiya Atae、Hino Ryosuke、Hanada Shuichi、Jo Tatsuro、Tsukasaki Kunihiro、Moriuchi Yukiyoshi、Sueoka Eisaburo、Yoshida Shinichiro、Suzushima Hitoshi、Miyahara Masaharu、Yamashita Kiyoshi、Eto Tetsuya、Suzumiya Junji、Tamura Kazuo
    • Journal Title

      Blood

      Volume: 130 Issue: 1 Pages: 39-47

    • DOI

      10.1182/blood-2017-01-757542

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A prognostic index for chronic- and smoldering-type adult T-cell leukemia-lymphoma2017

    • Author(s)
      Katsuya H, Shimokawa M, Ishitsuka K, Kawai K, Amano M, Utsunomiya A, Hino R, Hanada S, Jo T, Tsukasaki K, Moriuchi Y, Sueoka E, Yoshida S, Suzushima H, Miyahara M, Yamashita K, Eto T, Suzumiya J, Tamura K.
    • Journal Title

      Blood

      Volume: -

    • NAID

      40021603060

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] FoxP3-positive T cell lymphoma arising in non-HTLV1 carrier: clinicopathological analysis of 11 cases of PTCL-NOS and 2 cases of mycosis fungoides.2016

    • Author(s)
      Satou A, Asano N, Kato S, Katsuya H, Ishitsuka K, Elsayed AA, Nakamura S.
    • Journal Title

      Histopathology

      Volume: 68 Issue: 7 Pages: 1099-1108

    • DOI

      10.1111/his.12885

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Application of targeted enrichment to next-generation sequencing of retroviruses integrated into the host human genome.2016

    • Author(s)
      Miyazato P, Katsuya H, Fukuda A, Uchiyama Y, Matsuo M, Tokunaga M, Hino S, Nakao M, and Satou Y*.
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 28324-28324

    • DOI

      10.1038/srep28324

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Transcriptional and Epigenetic Regulatory Mechanism of HTLV-1 provirus.2016

    • Author(s)
      Miyazato P, Matsuo M, Katsuya H, and Satou Y*.
    • Journal Title

      Viruses 8(6), 171, 2016

      Volume: 8 Issue: 6 Pages: 171-171

    • DOI

      10.3390/v8060171

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Targeted Enrichment: A Novel Approach to Analyze the Integrated HTLV-1 Provirus through Next-Generation Sequencing2017

    • Author(s)
      Paola Miyazato, Hiroo Katsuya, Asami Fukuda, Yoshikazu Uchiyama, Misaki Matsuo, Michiyo Tokunaga, Shinjiro Hino, Mitsuyoshi Nakao, Yorifumi Satou
    • Organizer
      第 18回国際ヒトレトロウイルス HTLV会議
    • Place of Presentation
      ホテルグランドアーク半蔵門 (東京都千代田区)
    • Year and Date
      2017-03-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Possible Involvement of YB-1 in the Abnormal Nuclear Shape of Adult T-cell Leukemia/ Lymphoma Cells2017

    • Author(s)
      Hiroo Katsuya, Misaki Kakoki, Takafumi Noguchi, Yuki Inada, Paola Miyazato, Misaki Matsuo, Hiroyuki Hata, Tokio Tani, Yorifumi Satou
    • Organizer
      第 18回国際ヒトレトロウイルス HTLV会議
    • Place of Presentation
      ホテルグランドアーク半蔵門 (東京都千代田区)
    • Year and Date
      2017-03-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Phosphatidylinositol 3-kinase-δ (PI3k-δ) is a potential therapeutic target in adult T-cell leukemia-lymphoma2017

    • Author(s)
      Hiroo Katsuya, Lucy B. M. Cook, Aileen G. Rowan, Graham P. Taylor, Charles R. M. Bangham
    • Organizer
      第 18回国際ヒトレトロウイルス HTLV会議
    • Place of Presentation
      ホテルグランドアーク半蔵門 (東京都千代田区)
    • Year and Date
      2017-03-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 次世代シークエンスによるヒト化マウスHIV-1感染モデルにおけるウイルス感染細胞クローン動態解析2017

    • Author(s)
      佐藤賢文、勝屋弘雄、福田麻美、三沢尚子、伊東潤平、内山良一、宮里パオラ、Mohammad S Islam、Ariberto Fassati、Charles RM Bangham、小柳義夫、佐藤圭
    • Organizer
      第27回抗ウイルス療法学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Phosphatidylinositol 3-kinase-δ (PI3k-δ) is a potential therapeutic target in adult T-cell leukemia-lymphoma2017

    • Author(s)
      Hiroo Katsuya, Misaki Kakoki, Takahumi Noguchi, Yuki Inada, Paola Miyazato, Misaki Matsuo, Hiroyuki Hata, Tokio Tani, Yorifumi Satou
    • Organizer
      第4回日本HTLV-1学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Integral transcriptomic and epigenetic analyses of HTLV-1 proviruses in infected cell2017

    • Author(s)
      宮里パオラ、タン ベンジー ジェック ヤン、徳永美知代、松尾美沙希、勝屋弘雄、稲田優紀、佐藤賢文
    • Organizer
      第4回日本HTLV-1学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] HTLV-1新規エンハンサーの分子メカニズムおよび組み込み部位周辺宿主ゲノムとの機能的相互作用解析2017

    • Author(s)
      松尾美沙希、宮里パオラ、勝屋弘雄、稲田優紀、徳永雅仁、宇都宮與、野坂生郷、畑裕之、佐藤賢文
    • Organizer
      第4回日本HTLV-1学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Possible involvement of YB-1 in abnormal nuclear shape of adult T-cell leukemia-Iymphoma cells2017

    • Author(s)
      Misaki Kakoki, Hiroo Katsuya, Takafumi Noguchi, Yuki Inada, Paola Miyazato, Misaki Matsuo, Benjy Tan Jek Yang, Islam Mohammad Saiful, Hiroyuki Hata, Tokio Tani, Yorifumi Satou
    • Organizer
      第4回日本HTLV-1学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Possible involvement of YB-1 in abnormal nuclear shape of adult T-cell leukemia-Iymphoma cells2017

    • Author(s)
      Misaki Kakoki, Hiroo Katsuya, Takafumi Noguchi, Yuki Inada, Paola Miyazato, Misaki Matsuo, Masahito Tokunaga, Atae Utsunomiya, Hiroyuki Hata, Tokio Tani, Yorifumi Satou
    • Organizer
      第79回日本血液学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Highly sensitive viral RNA-seq is a powerful tool to analyze the viral transcripts in HTLV-1 infected individua2017

    • Author(s)
      稲田 優紀、勝屋 弘雄、宮里 パオラ、Benjy Tan Jek Yong、岩瀬 早織、鹿子木 実咲、松尾 美沙希、Islam Mohammad Saiful、徳永 まさとし、佐藤 知雄、畑 裕之、山野 嘉久、宇都宮 與、佐藤 賢文
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Identification and molecular characterization of a new HTLV-1 enhancer2017

    • Author(s)
      松尾美沙希、宮里 パオラ 、勝屋弘雄、稲田優紀、徳永 雅仁、宇都宮 與、野坂 生郷 、畑裕之、佐藤 賢文
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Highly sensitive viral RNA-seq is a powerful tool to analyze the viral transcripts in HTLV-1-infected individuals2017

    • Author(s)
      Yuki Inada, Hiroo Katsuya, Paola Miyazato, Benjy Tan Jek Yang, Saori Iwase, Misaki Kakoki, Misaki Matsuo, Islam Mohammad Saiful, Masahito Tokunaga, Hiroyuki Hata, Yoshihisa Yamano, Atae Utsunomiya, Yorifumi Satou
    • Organizer
      The 59th American Society of Hematology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 転写調節メカニズムの解明へ向けたHTLV-1感染細胞のプロウイルストランスクリプトーム解析(Transcriptomic analysis of HTLV-1 proviruses in infected cells: hints to elucidate the mechanisms of transcriptional regulation)2017

    • Author(s)
      宮里パオラ、タン ベンジー ジェック ヤン、徳永美知代、勝屋弘雄、松尾美沙希、稲田優紀、伊東潤平、佐藤賢文
    • Organizer
      第40回日本分子生物学会年会
    • Related Report
      2017 Annual Research Report

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Published: 2016-04-21   Modified: 2019-03-29  

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