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Elucidation of mechanisms of germ cell reprogramming and establishment of the procedure to control epigenome.

Research Project

Project/Area Number 21780269
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Basic veterinary science/Basic zootechnical science
Research InstitutionThe Institute of Physical and Chemical Research

Principal Investigator

INOUE Kimiko  The Institute of Physical and Chemical Research, 遺伝工学基盤技術室, 専任研究員 (70360500)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords核移植クローン / エピゲノム / 遺伝子発現 / X染色体 / H3K9me2 / DNAマイクロアレイ / Xist / 体細胞核移植クローン / 初期化 / LOCKs / 体細胞クローン胚 / Xist遺伝子
Research Abstract

To improve understanding of the low efficiency of somatic cell nuclear transfer (SCNT), we performed global transcription analysis of mouse SCNT blastocysts. Many of the downregulated genes (21/39) identified in SCNT embryos were located on the X chromosome. When the downregulation of X-linked genes in SCNT embryos was corrected by using Xist-deficient donor cells, the birth rates increased 8- to 9-fold. Thus, SCNT may be significantly improved by correcting epigenetic errors specific for SCNT.
In the next series of experiments, to understand the cause of consistent downregulation in the region of A7.2 and F3 on X chromosome (XqA7.2/F3) in SCNT blastocysts, we analyzed repressive modification, dimethylation of histone H3 lysine 9 (H3K9me2), with chromatin immunoprecipitation-on-chip data from cumulus cells. The results showed that H3K9me2 was broadly enriched in XqA7.2/F3 and formed tissue-specific blocks called as large organized chromatin K9 modification (LOCKs). These data suggested that downregulation of XqA7.2/F3 was caused by failure of reprogramming of LOCKs after nuclear transfer.

Report

(3 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • Research Products

    (22 results)

All 2011 2010 2009 Other

All Journal Article (9 results) (of which Peer Reviewed: 6 results) Presentation (4 results) Book (3 results) Remarks (5 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Impeding Xist expression from the active X chromosome improves mouse somatic cell nuclear transfer2010

    • Author(s)
      Inoue K, Kohda T, Sugimoto M, Sado T, Ogonuki N, Matoba S, Shiura H, Ikeda R, Mochida K, Fujii T, Sawai K, Otte A.P,Tian C., X, Yang X,Ishino F, Abe K, aOgura A
    • Journal Title

      Science. 330

      Pages: 496-499

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 活性X染色体からのXist遺伝子の発現の抑制はマウス体細胞クローンの効率を改善する2010

    • Author(s)
      井上貴美子, 小倉淳郎
    • Journal Title

      ライフサイエンス新着論文レビュー 1190

      Pages: 1-6

    • Related Report
      2010 Final Research Report
  • [Journal Article] Impeding Xist expression from the active X chromosome improves mouse somatic cell nuclear transfer2010

    • Author(s)
      K Inoue, et al.
    • Journal Title

      Science

      Volume: 330 Pages: 496-499

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 活性X染色体からのXist遺伝子の発現の抑制はマウス体細胞クローンの効率を改善する2010

    • Author(s)
      井上貴美子、小倉淳郎
    • Journal Title

      ライフサイエンス新着論文レビュー

      Volume: 1190

    • Related Report
      2010 Annual Research Report
  • [Journal Article] 核移植によるリプログラミング2010

    • Author(s)
      小倉淳郎、井上貴美子
    • Journal Title

      細胞

      Volume: 42 Pages: 489-493

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Sex-reversed somatic cell cloning in the mouse2009

    • Author(s)
      Inoue K, Ogonuki N, Mekada K, Yoshiki A, Sado T, Ogura A
    • Journal Title

      J.Reprod. Dev.55

      Pages: 566-569

    • NAID

      10025616710

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Embryonic Rather than Extraembryonic Tissues Have More Impact on the Development of Placental Hyperplasia in Cloned Mice2009

    • Author(s)
      Miki H, Wakisaka N, Inoue K, Ogonuki N, Mori M, Kim J, Ohta A, Ogura A
    • Journal Title

      Placenta. 30

      Pages: 543-546

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sex-reversed somatic cell cloning in the mouse2009

    • Author(s)
      K Inoue, et al
    • Journal Title

      J.Reproduction and Development

      Volume: 55 Pages: 566-569

    • NAID

      10025616710

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Embryonic rather than extraembryonic tissues have more impact on the development of placental hyperplasia in cloned mice2009

    • Author(s)
      H.Miki, et al
    • Journal Title

      Placenta

      Volume: 30 Pages: 543-546

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Sex-reversed somatic cell cloning in the mouse2009

    • Author(s)
      K Inoue
    • Organizer
      Asian Reproductive Biotechnology Society
    • Place of Presentation
      Siem Reap, Cambodia
    • Year and Date
      2009-11-16
    • Related Report
      2009 Annual Research Report
  • [Presentation] 体細胞核移植胚盤胞期胚に観察される遺伝子発現異常の解析2009

    • Author(s)
      井上貴美子
    • Organizer
      第102回日本繁殖生物学会
    • Place of Presentation
      近畿大学、奈良市
    • Year and Date
      2009-09-12
    • Related Report
      2009 Annual Research Report
  • [Presentation] Sex-reversed somatic cell cloning in the mouse, 6th Annual Conference of Asian Reproductive Biotechnology Society 20092009

    • Author(s)
      Inoue K, Ogonuki N, Mekada K, Yoshiki A, Sado T, OguraA
    • Organizer
      Seam Reap City, Cambodia, Nov
    • Related Report
      2010 Final Research Report
  • [Presentation] 体細胞核移植胚盤胞期胚に観察される遺伝子発現異常の解析2009

    • Author(s)
      井上貴美子, 越後貫成美, 幸田尚, 佐渡敬, 石野史敏, 小倉淳郎
    • Organizer
      第102回日本繁殖生物学会大会
    • Place of Presentation
      奈良
    • Related Report
      2010 Final Research Report
  • [Book] 遺伝子の導入法とノックアウト法,生命の誕生に向けて(第二版)2011

    • Author(s)
      小倉淳郎, 井上貴美子
    • Publisher
      近代出版
    • Related Report
      2010 Final Research Report
  • [Book] 生命の誕生に向けて(第2版)2011

    • Author(s)
      小倉淳郎、井上貴美子
    • Total Pages
      303
    • Publisher
      近代出版
    • Related Report
      2010 Annual Research Report
  • [Book] 核移植によるリプログラミング,細胞422010

    • Author(s)
      小倉淳郎, 井上貴美子
    • Related Report
      2010 Final Research Report
  • [Remarks] ホームページ等

    • Related Report
      2010 Final Research Report
  • [Remarks] 発表論文は下記URLにてプレスリリースを行った。:

    • URL

      http://www.riken.jp/r-world/info/release/press/2010/100917/index.html

    • Related Report
      2010 Final Research Report
  • [Remarks] また所属研究室HPにて情報を公開している。

    • URL

      http://www.brc.riken.jp/lab/kougaku/

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://www.riken.jp/r-world/info/release/press/2010/100917/index.html

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.brc.riken.jp/lab/kougaku/

    • Related Report
      2009 Annual Research Report
  • [Patent(Industrial Property Rights)] X染色体遺伝子の発現改変技術を用いた体細胞クローン胚および産子の作出2010

    • Inventor(s)
      小倉淳郎、井上貴美子、幸田尚、石野史敏
    • Industrial Property Rights Holder
      小倉淳郎、井上貴美子、幸田尚、石野史敏
    • Industrial Property Number
      2010-197583
    • Filing Date
      2010-09-03
    • Related Report
      2010 Annual Research Report 2010 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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