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肝細胞分化におけるエピゲノム修飾制御に関する研究

Publicly Offered Research

Project AreaMolecular mechanisms of cell fate determination in the cells that undergo stepwise differentiation to multiple pathways
Project/Area Number 23118508
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionThe University of Tokyo

Principal Investigator

油谷 浩幸  東京大学, 先端科学技術研究センター, 教授 (10202657)

Project Period (FY) 2011-04-01 – 2013-03-31
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
Fiscal Year 2012: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2011: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Keywords細胞系譜 / エピゲノム / クロマチン / DNAメチル化 / 細胞分化 / 転写制御 / 心筋分化
Outline of Annual Research Achievements

クロマチン制御因子がゲノムに作用する際にはクロマチンリモデリングによりchromatin accessibilityが変化すると考えられることから、エピゲノム標識を手がかりとして肝細胞分化をはじめとする細胞運命制御に関わるゲノム領域および制御因子の同定を進めた。第一に、Infiniumアレイを用いた包括的なDNAメチル化解析によりAPOA1をはじめとする肝特異的に発現する遺伝子のプロモーター領域のDNA脱メチル化が徐々に拡大することが認められ、転写活性化に関わると考えられた。さらに脱メチル化に関わるヒドロキシメチルシトシン(hmC)の局在についてhmCに対する抗体を用いた免疫沈降産物を次世代シーケンサーで解析した。第二に、Wnt刺激による分化誘導に伴い、細胞系譜特異的な制御因子によりaccessibilityが変動する領域をFAIRE-seq法によって抽出した。時期特異的に認められるFAIRE陽性領域は、転写開始点に加えてヒストンH3K4モノメチル化およびK27アセチル化を特徴とするエンハンサー領域に存在し、分化誘導に伴う変動が観察された。時期特異的な陽性領域に濃縮された塩基配列モチーフを抽出したところ、ES細胞ではOCT4/SOX2というような幹細胞特異的因子の結合配列が認められたのに対して、Wnt刺激後はTCFの結合モチーフが認められ、βカテニンの結合によってリモデリングが生じたことが認められた。さらにhmCは細胞分化に伴い出現するFAIRE陽性となる領域に一時的に出現する傾向が認められた。

Research Progress Status

24年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

24年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (20 results)

All 2013 2012 2011 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (10 results) (of which Invited: 1 results) Remarks (2 results)

  • [Journal Article] The role of NF-κB signaling in the maintenance of pluripotency of human induced pluripotent stem cells2013

    • Author(s)
      Takase O, Yoshikawa M, Idei M, Hirahashi J, Fujita T, Takato T, Isagawa T, Nagae G, Suemori H, Aburatani H, Hishikawa K
    • Journal Title

      PLoS One

      Volume: 8(2) Issue: 2 Pages: e56399-e56399

    • DOI

      10.1371/journal.pone.0056399

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The early retinal progenitor-expressed gene Sox11 regulates the timing of the differentiation of retinal cells2013

    • Author(s)
      Usui, A. et al.
    • Journal Title

      Development

      Volume: 140 Issue: 4 Pages: 740-750

    • DOI

      10.1242/dev.090274

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CDX1 directs gastric intestinal metaplasia via induction of stemness-associated reprogramming factors SALL4 and KLF52012

    • Author(s)
      Fujii, Y.
    • Journal Title

      Proc. Natl. Acad. Sci.USA

      Volume: 109 Issue: 50 Pages: 20584-20589

    • DOI

      10.1073/pnas.1208651109

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Essential roles of the histone methyltransferase ESET in the epigenetic control of neural progenitor cells during development.2012

    • Author(s)
      Tan, S.-L., Nishi, M., Ohtsuka, T., Matsui, T., Takemoto, K., Kamio-Miura, A., Aburatani, H., Shinkai, Y., and Kageyama, R.
    • Journal Title

      Development

      Volume: 139 Issue: 20 Pages: 3806-3816

    • DOI

      10.1242/dev.082198

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dynamic change of chromatin conformation in response to hypoxia enhances the expression of GLUT3 (SLC2A3) by cooperative interaction of hypoxia-inducible factor 1 and KDM3A.2012

    • Author(s)
      Mimura I
    • Journal Title

      Mol Cell Biol.

      Volume: Aug;32(15) Issue: 15 Pages: 3018-3032

    • DOI

      10.1128/mcb.06643-11

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cell type-specific target selection by combinatorial binding of Smad2/3 proteins and hepatocyte nuclear factor 4α in HepG2 cells2011

    • Author(s)
      Kanki Y, Kohro T, Jiang S, Tsutsumi S, Mimura I, Suehiro JI,Wada Y, Ohta Y, Ihara S, Iwanari H, Naito M, Hamakubo T,Aburatani H, Kodama T, Minami T
    • Journal Title

      EMBO J

      Volume: 286 Issue: 34 Pages: 29848

    • DOI

      10.1074/jbc.m110.217745

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gene expression profiling of mouse growth plate cartilage by laser microdissection and microarray analysis2011

    • Author(s)
      Isshiki H, Aburatani H, et al
    • Journal Title

      J Orthop Sci

      Volume: 16 Issue: 5 Pages: 670-2

    • DOI

      10.1007/s00776-011-0119-2

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epigenetic regulation of osteoclast differentiation: Possible involvement of Jmjd3 in the histone demethylation of Nfatc12011

    • Author(s)
      Yasui T, Aburatani H, et al
    • Journal Title

      J Bone Miner Res

      Volume: 26 Issue: 11 Pages: 2665

    • DOI

      10.1002/jbmr.464

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] Chromatin dynamics during cardiomyocyte differentiation2012

    • Author(s)
      油谷浩幸
    • Organizer
      International Symposium on genetic and epigenetic control of cell fate
    • Place of Presentation
      Kyoto
    • Year and Date
      2012-11-06
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Genome-wide profiling of promoter methylation identifies distinct subgroups in hepatocellular carcinoma.2012

    • Author(s)
      Nagae G
    • Organizer
      The 71th Japan Cancer Association Annual Meeting
    • Place of Presentation
      Sapporo
    • Year and Date
      2012-09-20
    • Related Report
      2012 Annual Research Report
  • [Presentation] エピゲノム解析の現状&心筋分化のエピゲノム・ダイナミクス2012

    • Author(s)
      油谷浩幸
    • Organizer
      第5回iPS細胞・再生医学研究会
    • Place of Presentation
      京都(招待講演)
    • Year and Date
      2012-02-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] エピゲノム解析とトランスレーショナル研究2012

    • Author(s)
      油谷浩幸
    • Organizer
      第10回がん・エピゲノム研究会
    • Place of Presentation
      仙台(招待講演)
    • Year and Date
      2012-01-18
    • Related Report
      2011 Annual Research Report
  • [Presentation] エピゲノム解析からせまる循環器研究2011

    • Author(s)
      油谷浩幸
    • Organizer
      第11回Cardiovascular Frontier Conference
    • Place of Presentation
      東京(招待講演)
    • Year and Date
      2011-11-19
    • Related Report
      2011 Annual Research Report
  • [Presentation] エピゲノム解析とゲノム医療2011

    • Author(s)
      油谷浩幸
    • Organizer
      第29回千駄木内分泌懇話会
    • Place of Presentation
      東京(招待講演)
    • Year and Date
      2011-10-20
    • Related Report
      2011 Annual Research Report
  • [Presentation] Regulatory genomics2011

    • Author(s)
      油谷浩幸
    • Organizer
      IMSUT&RCAST GCOE symposium
    • Place of Presentation
      東京(招待講演)
    • Year and Date
      2011-07-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] がんエピゲノム創薬2011

    • Author(s)
      油谷浩幸
    • Organizer
      第10回バイオテクノロジー国際会議
    • Place of Presentation
      東京(招待講演)
    • Year and Date
      2011-06-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] エピゲノム解析2011

    • Author(s)
      油谷浩幸
    • Organizer
      日本エピジェネティクス研究会
    • Place of Presentation
      熊本(招待講演)
    • Year and Date
      2011-05-19
    • Related Report
      2011 Annual Research Report
  • [Presentation] エピゲノム修飾の包括的解析によるがん創薬・バイオマーカー探索2011

    • Author(s)
      油谷浩幸
    • Organizer
      第100回日本病理学会総会
    • Place of Presentation
      横浜(招待講演)
    • Year and Date
      2011-04-30
    • Related Report
      2011 Annual Research Report
  • [Remarks] ゲノムサイエンス分野ホームページ

    • URL

      http://www.genome.rcast.u-tokyo.ac.jp/

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.genome.rcast.u-tokyo.ac.jp/

    • Related Report
      2011 Annual Research Report

URL: 

Published: 2011-04-06   Modified: 2018-03-28  

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