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Establishment of silent chromatin in mammals

Research Project

Project/Area Number 20370004
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Genetics/Genome dynamics
Research InstitutionNational Institute of Genetics

Principal Investigator

SADO Takashi  National Institute of Genetics, 生体防御医学研究所, 准教授 (70321601)

Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2010: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2009: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2008: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Keywords遺伝学 / ゲノム / 発生・分化 / 遺伝子
Research Abstract

X chromosome inactivation (X-inactivation) in female mammals is triggered by differential upregulation of the Xist gene on one of the two X chromosomes and subsequent coating of the X in cis with its noncoding transcripts. Although targeted mutation clearly showed that Xist is essential for X-inactivation to occur in cis, the molecular mechanism by which Xist RNA induces chromosome silencing is largely unknown. Here, we demonstrate that an Xist mutant generated previously by gene targeting, Xist^<IVS> is unique in that it retains a partial function to silence the X chromosome. Although Xist^<IVS> is differentially upregulated and its mutated transcript coats the X chromosome in cis in embryonic and extraembryonic tissues, X-inactivation thus initiated does not seem to be fully established. The state of such incomplete inactivation is probably unstable and the mutated X apparently ends up reactivated in a subset of extraembryonic tissues and, perhaps, early epiblastic cells. Xist^<IVS>, which can be referred to as a partial loss of function mutation, would provide an opportunity to dissect the molecular mechanism of Xist RNA-mediated chromosome silencing.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (40 results)

All 2011 2010 2009 2008 Other

All Journal Article (12 results) (of which Peer Reviewed: 12 results) Presentation (26 results) Remarks (2 results)

  • [Journal Article] Role for piRNAs and non-coding RNA in de novo DNA methylationof the imprinted mouse Rasgrfl locus.2011

    • Author(s)
      Watanabe, T., Tomizawa, S., Mitsuya, K., Totoki, Y., Yamamoto, Y., Kuramochi-Miyagawa, S., Iida, N., Hoki, Y., Murphy, P.J., Toyoda, A., Gotoh, K., Hiura, H., Arima, T., Fujiyama, A., Sado, T., Shibata, T., Nakano, T., Lin, H., Ichiyanagi, K., Soloway, P.D., Sasaki, H.
    • Journal Title

      Science Vol.332

      Pages: 848-852

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] MitoPLD is a mitochondrial protein essential for nuage formation and piRNA biogenesis in the mouse germline.2011

    • Author(s)
      Watanabe, T., Chuma, S. Yamamoto, Y., Kuramochi-Miyagawa, S., Totoki, Y., Toyoda, A., Hoki, Y., Fujiyama, A., Shibata, T., Sado, T., Noce, T., Nakano, T., Nakatsuji, N., Lin, H., Sasaki, H.
    • Journal Title

      Developmental Cell vol.20

      Pages: 364-375

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role for piRNAs and non-coding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus.2011

    • Author(s)
      Watanabe, et al.
    • Journal Title

      Science

      Volume: (In press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Incomplete X-inactivation initiated by a hypomorphic Xist allele in the mouse.2011

    • Author(s)
      Hoki, et al.
    • Journal Title

      Development

      Volume: (In press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MitoPLD is a mitochondrial protein essential for nuage formation and piRNA biogenesis in the mouse germline.2011

    • Author(s)
      Watanabe, et al.
    • Journal Title

      Developmental Cell

      Volume: 20 Pages: 364-375

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impeding Xist Expression from the Active X Chromosome Improves Mouse Somatic Cell Nuclear Transfer.2010

    • 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, AP., Tian, XC., Yang, X., Ishino, F., Abe, K., Ogura, A.
    • Journal Title

      Science Vol.330

      Pages: 496-499

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Impeding Xist Expression from the Active X Chromosome Improves Mouse Somatic Cell Nuclear Transfer.2010

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

      Science

      Volume: 330 Pages: 496-499

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sex-reversed somatic cell cloning in the mouse.2009

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

      J. Reprod. Dev. 55

      Pages: 566-569

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A proximal conserved repeat in the Xist gene is essential as a genomic element for X-inactivation in mouse.2009

    • Author(s)
      Hoki, et al.
    • Journal Title

      Development. 136

      Pages: 139-146

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dicer regulates Xist promoter methylation in ES cells indirectly through transcriptional control of Dnmt3a.2008

    • Author(s)
      Nesterova, et al.
    • Journal Title

      Epigenetics and Chromatin 1

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] De novo DNA methylation independent establishment of maternalimprint on X chromosome in mouse oocytes.2008

    • Author(s)
      Chiba, et al.
    • Journal Title

      genesis 46

      Pages: 768-774

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Incomplete X-inactivation initiated by a hypomorphic Xist allele in the mouse.

    • Author(s)
      Hoki, Y., Ikeda, R., Mise, N., Sakata, Y., Ohhata, T., Sasaki, H., Abe, K., Sado, T.
    • Journal Title

      Development 印刷中

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Presentation] A Partial Loss of Function Mutation in the Mechanism of X Chromosome Inactivation.2010

    • Author(s)
      佐渡敬
    • Organizer
      The 19th CDB Meeting
    • Place of Presentation
      兵庫
    • Related Report
      2010 Final Research Report
  • [Presentation] 胚体外組織における父由来X染色体のインプリント2010

    • Author(s)
      尼川裕子, 保木裕子, 佐々木裕之, 深川竜郎, 佐渡敬
    • Organizer
      第4回日本エピジェネティクス研究会
    • Place of Presentation
      米子
    • Related Report
      2010 Final Research Report
  • [Presentation] Xist RNAの5'領域のX染色体不活化における役割2010

    • Author(s)
      酒田祐佳, 尼川裕子, 保木裕子, 佐々木裕之, 佐渡敬
    • Organizer
      第4回日本エピジェネティクス研究会
    • Place of Presentation
      米子
    • Related Report
      2010 Final Research Report
  • [Presentation] X染色体不活性化の部分的機能欠損変異の解析2010

    • Author(s)
      佐渡敬, 保木裕子, 池田理恵子, 三瀬名丹, 大畑樹也, 佐々木裕之, 阿部訓也
    • Organizer
      第12回日本RNA学会年会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] Xist RNAの作用機序の理解へ向けて2010

    • Author(s)
      佐渡敬
    • Organizer
      日本遺伝学会第82回大会
    • Place of Presentation
      札幌
    • Related Report
      2010 Final Research Report
  • [Presentation] Xist RNAの5'領域のX染色体不活化における役割2010

    • Author(s)
      酒田祐佳, 尼川裕子, 保木裕子, 佐々木裕之, 佐渡敬
    • Organizer
      日本遺伝学会第82回大会
    • Place of Presentation
      札幌
    • Related Report
      2010 Final Research Report
  • [Presentation] Xist RNAの機能不全が招くX染色体不活性化の異常2010

    • Author(s)
      佐渡敬
    • Organizer
      第33回日本分子生物学会年会,第83回日本生化学会大会
    • Place of Presentation
      神戸
    • Related Report
      2010 Final Research Report
  • [Presentation] Xist RNAの5'領域のX染色体不活性化における役割2010

    • Author(s)
      酒田祐佳, 尼川裕子, 保木裕子, 佐々木裕之, 佐渡敬
    • Organizer
      第33回日本分子生物学会年会,第83回日本生化学会大会
    • Place of Presentation
      神戸
    • Related Report
      2010 Final Research Report
  • [Presentation] A Partial Loss of Function Mutation in the Mechanism of X Chromosome Inactivation2010

    • Author(s)
      Sado, T.
    • Organizer
      The 19th CDB Meeting
    • Place of Presentation
      兵庫
    • Related Report
      2010 Annual Research Report
  • [Presentation] Xist RNAの5'領域のX染色体不活化における役割2010

    • Author(s)
      酒田祐佳, 他4名
    • Organizer
      第4回 日本エピジェネティクス研究会
    • Place of Presentation
      鳥取
    • Related Report
      2010 Annual Research Report
  • [Presentation] 胚体外組織における父由来X染色体のインプリント2010

    • Author(s)
      尼川裕子, 他4名
    • Organizer
      第4回 日本エピジェネティクス研究会
    • Place of Presentation
      鳥取
    • Related Report
      2010 Annual Research Report
  • [Presentation] X染色体不活性化の部分的機能欠損変異の解析2010

    • Author(s)
      佐渡敬, 他6名
    • Organizer
      第12回 日本RNA学会年会
    • Place of Presentation
      東京
    • Related Report
      2010 Annual Research Report
  • [Presentation] Xist RNAの作用機序の理解へ向けて2010

    • Author(s)
      佐渡敬
    • Organizer
      日本遺伝学会 第82回大会
    • Place of Presentation
      北海道
    • Related Report
      2010 Annual Research Report
  • [Presentation] Xist RNAの5'領域のX染色体不活化における役割2010

    • Author(s)
      酒田祐佳, 他4名
    • Organizer
      日本遺伝学会 第82回大会
    • Place of Presentation
      北海道
    • Related Report
      2010 Annual Research Report
  • [Presentation] Xist RNAの機能不全が招くX染色体不活性化の異常2010

    • Author(s)
      佐渡敬
    • Organizer
      第33回日本分子生物学会年会,第83回日本生化学会大会
    • Place of Presentation
      兵庫
    • Related Report
      2010 Annual Research Report
  • [Presentation] Xist RNAの5'領域のX染色体不活化における役割2010

    • Author(s)
      酒田祐佳, 他4名
    • Organizer
      第33回日本分子生物学会年会,第83回日本生化学会大会
    • Place of Presentation
      兵庫
    • Related Report
      2010 Annual Research Report
  • [Presentation] A partial loss of function mutation in the mechanism of X chromosome inactivation.2010

    • Author(s)
      Hoki, Y., et al.
    • Organizer
      Keystone Symposium(A8)
    • Place of Presentation
      Taos, NM(USA)
    • Related Report
      2009 Annual Research Report
  • [Presentation] Prolonged expression of Xist retards X chromosome reactivation in mouse germ line.2010

    • Author(s)
      Amakawa, Y., et al.
    • Organizer
      Keystone Symposium(A8)
    • Place of Presentation
      Taos, NM(USA)
    • Related Report
      2009 Annual Research Report
  • [Presentation] X染色体の不活性化の分子機構2009

    • Author(s)
      佐渡敬
    • Organizer
      第138回染色体研究会
    • Place of Presentation
      東京
    • Year and Date
      2009-06-13
    • Related Report
      2009 Annual Research Report
  • [Presentation] Toward the understanding of molecular events underlying X-inactivation.2009

    • Author(s)
      Sado, T.
    • Organizer
      The 24th Naito Conference on Nuclear Dynamics and RNA[II]
    • Place of Presentation
      札幌
    • Related Report
      2009 Annual Research Report
  • [Presentation] マウスのメス生殖細胞におけるXist発現消失時期の遅延はX染色体再活性化を遅らせる.2009

    • Author(s)
      尼川裕子, 他3名
    • Organizer
      日本遺伝学会第81回大会
    • Place of Presentation
      松本
    • Related Report
      2009 Annual Research Report
  • [Presentation] X染色体不活性化機構の部分的機能欠損変異2009

    • Author(s)
      保木裕子, 他3名
    • Organizer
      日本遺伝学会第81回大会
    • Place of Presentation
      松本
    • Related Report
      2009 Annual Research Report
  • [Presentation] 哺乳類のメス生殖細胞における不活性X染色体の再活性化2009

    • Author(s)
      佐渡敬
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸
    • Related Report
      2009 Annual Research Report
  • [Presentation] A partial loss of function mutation in the mechanism of X chromosome inactivation.2009

    • Author(s)
      保木裕子, 他3名
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2009 Annual Research Report
  • [Presentation] Prolonged expression of Xist retards X chromosome reactivation in mouse germ line.2009

    • Author(s)
      尼川裕子, 他3名
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2009 Annual Research Report
  • [Presentation] マウス胚におけるXist遺伝子発現制御2008

    • Author(s)
      佐渡敬, 保木裕子, 木村直美, 佐々木裕之
    • Organizer
      日本遺伝学会第80回大会
    • Place of Presentation
      名古屋大学
    • Year and Date
      2008-09-03
    • Related Report
      2008 Annual Research Report
  • [Remarks] ホームページ等

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://www.nig.ac.jp/hot/2008/sado0811-j.html

    • Related Report
      2008 Annual Research Report

URL: 

Published: 2008-04-01   Modified: 2016-04-21  

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