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Biological significance of developmental gene silencing of Dnmt3b.

Research Project

Project/Area Number 23651194
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Medical genome science
Research InstitutionOsaka University

Principal Investigator

AOTA Kiyoe (URA Kiyoe)  大阪大学, 医学系研究科, 准教授 (80289363)

Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsクロマチン / DNA メチル化 / Dnmt3b / DNAメチル化 / 心臓 / Nkx2-5 / 心臓形成
Research Abstract

Methylation of cytosine C5 of CpG dinucleotides is a characteristic DNA modification in many eukaryotic genomes that plays an important role in developmental gene regulation. DNA methylation is mediated by Dnmt1, Dnmt3a, and Dnmt3b, however, it is not known how each Dnmt selects target CpG sites in the genome and control gene silencing during development. Since Dnmt3b expresses specifically in ES cells and undifferentiated hematopoietic cells and repressed differentiated cells, we hypothesized that “developmental silencing of Dnmt3 is important for normal organogenesis”. To address this issue, we established Dnmt3b -conditional transgenic mice Tg-loxDnmt3b using Cre/lox system. Over expression of Dnmt3b repress cell proliferation and differentiation in ex vivo culture of hematopoietic stem cells. Furthermore, Tg-loxDnmt3b, Nkx2-5/Cre double mutant mice exhibited growth retardation. These results show that abnormal expression of Dnmt accelerate out of control of developmental gene expression.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (12 results)

All 2012 2011 Other

All Journal Article (4 results) (of which Peer Reviewed: 2 results) Presentation (7 results) Remarks (1 results)

  • [Journal Article] Impact of histone H4 lysine 20 methylation on 53BP1 responses to chromosomal double strand breaks2012

    • Author(s)
      Andrea H., Yinghua G., Anbazhagan R., Kiyoe U., Gunnar S., Anyong X., Jagesh S. and Ralph S
    • Journal Title

      PLoS ONE

      Volume: 7

    • Related Report
      2012 Final Research Report
  • [Journal Article] Impact of histone H4 lysine 20 methylation on 53BP1 responses to chromosomal double strand breaks.2012

    • Author(s)
      Andrea H., Yinghua G., Anbazhagan R., Kiyoe U., Gunnar S., Anyong X., Jagesh S. and Ralph S.
    • Journal Title

      PLoS ONE

      Volume: 7 Issue: 11 Pages: e49211-e49211

    • DOI

      10.1371/journal.pone.0049211

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DNA methyltransferase 3b preferentially associates with condensed chromatin.2011

    • Author(s)
      Kashiwagi K., Nimura K., *Ura K. and *Kaneda Y.
    • Journal Title

      Nucleic Acids Res

      Volume: 39 Pages: 874-888

    • Related Report
      2012 Final Research Report
  • [Journal Article] DNA methyltransferase 3b preferentially associates with condensed chromatin2011

    • Author(s)
      Kashiwagi K., Nimura K., Ura K., Kaneda Y.
    • Journal Title

      Nucleic Acids Res

      Volume: 39 Issue: 3 Pages: 874-888

    • DOI

      10.1093/nar/gkq870

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Histone H3 lysine 36 methyltransferase Whsc1 controls the programmed DNA-damage response during V(D)J recombination.2012

    • Author(s)
      Kiyoe Ura, Takafumi Yokota, Makiko Kajio, Atsushi Iwama and Yasufumi Kaneda.
    • Organizer
      The 8th 3R Symposium
    • Place of Presentation
      Awaji
    • Related Report
      2012 Annual Research Report
  • [Presentation] クロマチン高次構造上における相同組換え反応の解析2012

    • Author(s)
      町田晋一、高久誉大、小林航、越阪部晃永、立和名博昭、鈴木秀和、浦聖恵、井倉正枝、井倉毅、田代聡、胡桃坂仁志
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] 再構成クロマチンから疾患モデルマウスを用いたヒストン多種多様性の生物学的意義の探求2011

    • Author(s)
      浦 聖恵
    • Organizer
      構造エピジェゲノム研究会第3回ワークショップ(招待講演)
    • Place of Presentation
      横浜
    • Related Report
      2011 Research-status Report
  • [Presentation] ヒストンの多種多様性を介したエピジェネティク制御2011

    • Author(s)
      浦 聖恵
    • Organizer
      第5回日本エピジェネティクス研究会年会シンポジウム(招待講演)
    • Place of Presentation
      熊本
    • Related Report
      2011 Research-status Report
  • [Presentation] Regulation and Function of Histone Diversity in Development and Disease.2011

    • Author(s)
      浦 聖恵
    • Organizer
      第11回日本蛋白質科学会年会(招待講演)
    • Place of Presentation
      大阪
    • Related Report
      2011 Research-status Report
  • [Presentation] Mapping of DNaseI hypersensitive sites reveals hyperdynamic chromatin in pluripotent ES cells.2011

    • Author(s)
      Kiyoe Ura.
    • Organizer
      FASEB, Transcription and chromatin(招待講演)
    • Place of Presentation
      USA
    • Related Report
      2011 Research-status Report
  • [Presentation] Regulation and Function of Histone Diversity in Development Gene Regulation.2011

    • Author(s)
      Kiyoe Ura.
    • Organizer
      第35回日本分子生物学会(招待講演)
    • Place of Presentation
      横浜
    • Related Report
      2011 Research-status Report
  • [Remarks]

    • URL

      http://www.med.osaka-u.ac.jp/pub/gts/

    • Related Report
      2012 Final Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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