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染色体レベルでのDNAメチル化と転写相関によるリンパ系腫瘍発がん機構の解析

Research Project

Project/Area Number 19659244
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Hematology
Research InstitutionKyoto University

Principal Investigator

松岡 雅雄  Kyoto University, ウイルス研究所, 教授 (10244138)

Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2007: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordsエピジェネティクス / DNAメチル化 / 発がん / 白血病 / ゲノム
Research Abstract

1) Methylated CpG island amplification/representative difference assay (MCA/RDA)法を用いて正常Bリンパ球と比較して慢性リンパ性白血病細胞(CLL)細胞、悪性リンパ腫細胞(diffuse large cell lymphoma)において高・低メチル化しているDNA断片を網羅的に単離したところ、低メチル化DNAが多く同定された。低メチル化が集積した領域(1p36, 7p22.3, 9q34, 17q21, 19p13.3, 22q13.3)はBリンパ球で転写が亢進している部分と一致していた。この結果から転写がメチル化に影響を与えていることが示唆された。
2) 低メチル化が集積している領域にコードされる遺伝子群を検索したところTNF受容体ファミリークラスターが存在しており、CLL細胞株で、それらの遺伝子発現が増強されていることをRT-PCRで確認した。その中でBリンパ球の増殖に関連していることが予想される遺伝子に関してノックダウンの実験を行ったが、増殖に関して変化は認められなかった。
3) Bリンパ球系の腫瘍細胞(CLL, DLCL)で同様の低メチル化パターンが認められたことから細胞特異的な転写様式がメチル化に影響を与えていることが示唆された。このような領域特異的な転写調節機構に関してインスレーターのようなゲノムコンポーネントの存在が考えられる。

Report

(2 results)
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (16 results)

All 2008 2007

All Journal Article (13 results) (of which Peer Reviewed: 13 results) Presentation (3 results)

  • [Journal Article] Broad Anti-Retroviral Activity and Resistance Profile of a Novel Human Immunodeficiency Virus Integrase Inhibitor, Elvitegravir (JTK-303/GS-9137).2008

    • Author(s)
      Shimura K.
    • Journal Title

      J Virol. 82

      Pages: 764-774

    • Related Report
      2008 Annual Research Report 2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adult T-cell leukemia/lymphoma ; Hematopoietic stem cell transplantation ; allogeneic ; reducedintensity transplantation ; anti-thymocyte globulin ; graft versus-ATLL effect.2008

    • Author(s)
      Tanosaki R.
    • Journal Title

      Biology of Blood and Marrow Transplantation 14

      Pages: 702-708

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Potential link between alternative splicing of the NBS1 gene and the DNA damage/environmental stress.2008

    • Author(s)
      Takai K.
    • Journal Title

      Radiation Res. 170

      Pages: 33-40

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transcriptional control of spliced and unspliced HTLV-1 bZIP factor gene2008

    • Author(s)
      Yoshida M.
    • Journal Title

      J Virol. 82

      Pages: 9359-9368

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Roles for microRNAs, miR-93 and miR-130b, and TP53INP1 tumor suppressor in cell growth dysregulation by HTLV-12008

    • Author(s)
      Yeung ML.
    • Journal Title

      Cancer Res. 68

      Pages: 8976-8985

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Dual-Reporter Phenotypic Assay for Human Immunodeficiency Viruses.2008

    • Author(s)
      Kajiwara K.
    • Journal Title

      J Clin Microbiol. 46

      Pages: 792-795

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phenotypic and genotypic comparison of human T-cell leukemia virus type l reversetranscriptase from infected T-cell lines and patient samples.2007

    • Author(s)
      Mitchell MS.
    • Journal Title

      J Virol. 81

      Pages: 4422-4428

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Preferential Selection of HIL V-1 Provirus Lacking the 5'LTR during Oncogenesis.2007

    • Author(s)
      Miyazaki M.
    • Journal Title

      J Virol. 81

      Pages: 5714-5723

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Antiviral Activity against HIV-1, Intracellular Metabolism, and Effects on Human DNA Polymerases of 4'-Ethynyl-2-fluoro-2'-deoxyadenosine.2007

    • Author(s)
      Nakata H.
    • Journal Title

      Antimicrob. Agents Chemother. 51

      Pages: 2701-2708

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of adult T-cell leukemia in donor-derived human T-cell leukemia virus type I-infected T cells after allogeneic bone marrow transplantation.2007

    • Author(s)
      Tamaki H.
    • Journal Title

      Leukemia 21

      Pages: 1594-1596

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cooperation of NF-κB2/p100 activation and the PDZ domain binding motif signal in human T-cell leukemia virus type I (HTLV) Taxl but not HTLV-2 Tax2 is crucial for interleukin-2 independent growth transformation of a T cell line.2007

    • Author(s)
      Higuchi M
    • Journal Title

      J Virol. 81

      Pages: 11900-11907

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] GANP suppresses DNA recombination, measured by direct-repeat beta-galactosidase gene construct, but does not suppress the type of recombination applying to immunoglobulin genes in mammalian cells.2007

    • Author(s)
      Yoshida M.
    • Journal Title

      Genes Cells 12

      Pages: 1205-1213

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heptad repeat-derived peptides block the protease-mediated direct entry from cell surface of SARS coronavirus but not entry via endosomal pathway.2007

    • Author(s)
      Ujike M.
    • Journal Title

      J Virol. 82

      Pages: 588-592

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Molecular pathogenesis and host immune response.2008

    • Author(s)
      Matsuoka M.
    • Organizer
      IID 2008 Satellite Workshop "Viras-associated Lymphomas"
    • Place of Presentation
      Kyoto, Japan (京都国際会館)
    • Year and Date
      2008-05-13
    • Related Report
      2008 Annual Research Report
  • [Presentation] Lentivirus integration and DNA repair.2008

    • Author(s)
      Matsuoka M.
    • Organizer
      Ataxia-Telangiectasia Workshop 2008.
    • Place of Presentation
      Otsu, Japan. (大津プリンスホテル)
    • Year and Date
      2008-04-22
    • Related Report
      2008 Annual Research Report
  • [Presentation] Clustering of hypomethylated DNA regions associated with transcriptional changes in B-CLL.2007

    • Author(s)
      Fan Jun.
    • Organizer
      第66回日本癌学会学術総会
    • Place of Presentation
      横浜(パシフィコ横浜)
    • Year and Date
      2007-10-03
    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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