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Gene regulation via dynamic change of chromosomal conformation of remote enhancers

Research Project

Project/Area Number 21247002
Research Category

Grant-in-Aid for Scientific Research (A)

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

Principal Investigator

SHIROISHI Toshihiko  国立遺伝学研究所, 系統生物研究センター, 教授 (90171058)

Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥44,720,000 (Direct Cost: ¥34,400,000、Indirect Cost: ¥10,320,000)
Fiscal Year 2011: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000)
Fiscal Year 2010: ¥15,470,000 (Direct Cost: ¥11,900,000、Indirect Cost: ¥3,570,000)
Fiscal Year 2009: ¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000)
Keywords遺伝学・ゲノム・進化・動物・発生 / 分化 / 遺伝 / ゲノム / 進化 / 動物 / 発生・分化 / 遺伝子発現制御 / 染色体ダイナミクス / 遠隔エンハンサー / 非翻訳保存配列 / 形態形成 / 進化発生学
Research Abstract

Sonic hedgehog(Shh) encodes a signaling protein that plays pivotal roles in vertebrate development. Comparison of genomic sequences across mammalian species and teleost fishes revealed four conserved non-coding sequences(CNCSs) that cluster in a region 600 to 900 kb upstream of the Shh promoter. These CNCSs drive regional transgenic lacZ reporter expression in the limb bud and the epithelial lining of the oral cavity, pharynx and larynx(lung/gut), recapitulating the endogenous Shh expression. Targeted elimination of each of the four CNCSs from the mouse genome results in loss of endogenous Shh expression in specific regions, corresponding to the expression pattern of the transgenic LacZ reporter, and leads to regional-specific defect. The results indicate that these CNCSs are tissue-specific long-range Shh enhancers. The 3D-FISH and 3C analyses showed that the Shh promoter-enhancer occurs in a tissue specific manner. Thus, chromosome dynamics is a common mechanism to regulate the tissue-specific Shh expression by the long-range enhancers.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (24 results)

All 2012 2011 2010 2009

All Journal Article (16 results) (of which Peer Reviewed: 16 results) Presentation (8 results)

  • [Journal Article] Prx-1 Expression in Xenopus laevis Scarless Skin-Wound Healing and Its Resemblance to Epimorphic Regeneration2011

    • Author(s)
      Yokoyama H, Maruoka T, Aruga A, Amano T, Ohgo S, Shiroishi T, Tamura K.
    • Journal Title

      J Invest Dermatol

      Volume: 132 Pages: 2477-2485

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ribosome-mediated specificity in hox mRNA translation and vertebrate tissue patterning2011

    • Author(s)
      Kondrashov N, Pusic A, Stumpf CR, Shimizu K, Hsieh AC, Xue S, Ishijima J, Shiroishi T, Barna M.
    • Journal Title

      Cell

      Volume: 145 Pages: 383-397

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ptch1-mediated dosage-dependent action of Shh signaling regulates neural progenitor development at late gestational stages2011

    • Author(s)
      Shikata Y, Okada T, Hashimoto M, Ellis T, Matsumaru D, Shiroishi T, Ogawa M, Wainwright B, Motoyama J.
    • Journal Title

      Dev Biol

      Volume: 349 Pages: 147-59

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prx-1 Expression in Xenopus laevis Scarless Skin-Wound Healing and Its Resemblance to Epimorphic Regeneration2011

    • Author(s)
      Yokoyama H
    • Journal Title

      J Invest Dermatol

      Volume: 131 Issue: 12 Pages: 477-485

    • DOI

      10.1038/jid.2011.223

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ptch1-mediated dosage-dependent action of Shh signaling regulates neural progenitor development at late gestational stages2011

    • Author(s)
      Shikata Y
    • Journal Title

      Dev Biol

      Volume: 349 Issue: 2 Pages: 147-159

    • DOI

      10.1016/j.ydbio.2010.10.014

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ptch1-mediated dosage-dependent action of Shh signaling regulates neural progenitor development at late gestational stages.2011

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

      Developmental Biology

      Volume: 349 Pages: 147-159

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anterior shift in gene expression precedes anteriormost digit formation in amniote limbs2010

    • Author(s)
      Uejima A, Amano T, Nomura N, Noro M, Yasue T, Shiroishi T, Ohta K, Yokoyama H, Tamura K.
    • Journal Title

      Dev Growth Differ

      Volume: 52 Pages: 223-234

    • NAID

      10027563906

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Anterior shift in gene expression precedes anteriormost digit formation in a mniote limbs.2010

    • Author(s)
      Uejima, A.
    • Journal Title

      Development Growth and Differentiation

      Volume: 52 Pages: 223-234

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Essential mesenchymal role of small GTPase Rac1 in interdigital programmed cell death during limb development2009

    • Author(s)
      Suzuki D, Yamada A, Amano T, Yasuhara R, Kimura A, Sakahara M, Tsumaki N, Takeda S, Tamura M, Nakamura M, Wada N, Nohno T, Shiroishi T, Aiba A, Kamijo R.
    • Journal Title

      Dev Biol

      Volume: 335 Pages: 396-406

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The disruption of Sox21-mediated hair shaft cuticle differentiation causes cyclic alopecia in mice2009

    • Author(s)
      Kiso M, Tanaka S, Saba R, Matsuda S, Shimizu A, Ohyama M, Okano HJ, Shiroishi T, Okano H, Saga Y.
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 106 Pages: 9292-9297

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chromosomal dynamics at the Shh locus : limb bud-specific differential regulation of competence and active transcription2009

    • Author(s)
      Amano T, Sagai T, Tanabe H, Mizushina Y, Nakazawa H, Shiroishi T.
    • Journal Title

      Dev Cell

      Volume: 16 Pages: 47-57

    • NAID

      120006576058

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] A cluster of three long-range enhancers directs regional Shh expression in the epithelial linings2009

    • Author(s)
      Sagai T, Amano T, Tamura M, Mizushina Y, Sumiyama K, Shiroishi T.
    • Journal Title

      Development

      Volume: 136 Pages: 1665-1674

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification and characterization of new long conserved noncoding sequences in vertebrates2009

    • Author(s)
      Sakuraba Y, Kimura T, Masuya H, Noguchi H, Sezutsu H, Takahasi KR, Toyoda A, Fukumura R, Murata T, Sakaki Y, Yamamura M, Wakana S, Noda T, Shiroishi T, Gondo Y.
    • Journal Title

      Mammal Genome

      Volume: 19 Pages: 703-712

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Specific expression of Gsta4 in mouse cochlear melanocytes : a novel role for hearing and melanocyte differentiation2009

    • Author(s)
      Uehara S, Izumi Y, Kubo Y, Wang CC, Mineta K, Ikeo K, Gojobori T, Tachibana M, Kikuchi T, Kobayashi T, Shibahara S, Taya C, Yonekawa H, Shiroishi T, Yamamoto H.
    • Journal Title

      Pigment Cell Melanoma Res

      Volume: 22 Pages: 111-119

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] A cluster of three long-range enhancers directs regional Shh expression in the epithelial linings2009

    • Author(s)
      嵯峨井知子
    • Journal Title

      Development 136

      Pages: 1665-1674

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chromosomal dynamics at the Shh locus : limb bud-specific differential regulation of competence and active transcription2009

    • Author(s)
      天野孝紀
    • Journal Title

      Developmental Cell 16

      Pages: 47-57

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Long-range enhancers directing regional Shh expression in the epithelial linings2012

    • Author(s)
      Shiroishi T.
    • Organizer
      The Hedgehog Meeting
    • Place of Presentation
      Singapore
    • Year and Date
      2012-03-20
    • Related Report
      2011 Final Research Report
  • [Presentation] Long-range enhancers regulate developmental Shh expression via chromosomal dynamics2010

    • Author(s)
      Shiroishi T.
    • Organizer
      EMBO Meeting
    • Place of Presentation
      Barcelona
    • Year and Date
      2010-09-07
    • Related Report
      2011 Final Research Report
  • [Presentation] Chromosome dynamics underlying regulation of developmental Shh expression2009

    • Author(s)
      Amano T, Tanabe H, Sagai T. and Shiroishi T.
    • Organizer
      第32回日本分子生物学会年会シンポジウム
    • Place of Presentation
      横浜
    • Year and Date
      2009-12-10
    • Related Report
      2011 Final Research Report
  • [Presentation] 染色体ダイナミクスを介したShh遺伝子の動的発現制御2009

    • Author(s)
      天野孝紀
    • Organizer
      日本遺伝学会第81回大会
    • Place of Presentation
      信州大学理学部
    • Year and Date
      2009-09-17
    • Related Report
      2009 Annual Research Report
  • [Presentation] 染色体ダイナミクスを介したShh遺伝子の動的発現制御2009

    • Author(s)
      天野孝紀,城石俊彦
    • Organizer
      日本遺伝学会第81回大会ワークショップ
    • Place of Presentation
      松本
    • Year and Date
      2009-06-18
    • Related Report
      2011 Final Research Report
  • [Presentation] A cluster of three long-range enhancers directs regional Shh expression in the epithelial linings2009

    • Author(s)
      嵯峨井知子
    • Organizer
      第42回日本発生生物学会
    • Place of Presentation
      第42回日本発生生物学会
    • Year and Date
      2009-05-29
    • Related Report
      2009 Annual Research Report
  • [Presentation] Long-range enhancer-promoter interaction via chromosomal dynamics at the Shh locus2009

    • Author(s)
      天野孝紀
    • Organizer
      23rd International Mammalian Genome Conference
    • Place of Presentation
      Hilton La Jolla Torrey Pines
    • Year and Date
      2009-05-29
    • Related Report
      2009 Annual Research Report
  • [Presentation] Long-range enhancer-promoter interaction via chromosomal dynamics at the Shh locus2009

    • Author(s)
      Amano, T., Sagai, T., Tanabe, H. and Shiroishi T.
    • Organizer
      23th INTERNATIONAL MOUSE GENOME CONFERENCE 2009
    • Place of Presentation
      La Jolla, San Diego, USA
    • Related Report
      2011 Final Research Report

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

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