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The structure and function of myogenic factors.

Research Project

Project/Area Number 02454151
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field General medical chemistry
Research InstitutionNational Institute of Neuroscience

Principal Investigator

NABESHIMA Yo-ichi  Dep.of Molecular Genetics, Director National Institute of Neuroscience, 神経研究所・遺伝子工学, 部長 (60108024)

Co-Investigator(Kenkyū-buntansha) MATSUZAKI Fumio  Dep. of Molecular Genetics, Section Chief National Institute of Neuroscience, 神経センター・神経研究所・遺伝子工学, 室長 (10173824)
FUJISAWA Atsuko  Dep. of Molecular Genyics, Section Chief National Institute of Neuroscience, 神経センター・神経研究所・遺伝子工学, 室長 (60209038)
Project Period (FY) 1990 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1992: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1991: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1990: ¥3,400,000 (Direct Cost: ¥3,400,000)
KeywordsMuscle Development / Myogenic Genes / 6HLH proteins / Transcriptional Regulation / Gene Targeting / Enhancer / Myogenin / Mysic light chain gene / MyoD family / E-box / トランスジェニックマウス / 筋分化制御因子 / bHLH / 転写調節 / エンハンサ- / MLC box / 筋細胞分化 / 遺伝子発現 / ミオシンアルカリ軽鎖 / MLC / CAvGボックス
Research Abstract

1) In order to analyze the roles of individual members of myogenic regulatory factors in myogenesis, we have investigated their effects on the transcription driven by the promoter of the chicken myosin alkali light chain (MLC1/3) gene. CMD1(MyoD) or c-myogenin, but cMRF4 activated transcription of reporter plasmid containing 3.4kb upstream region of MLC1 gene in primary fibriblasts. The activation by MyoD or myogenin was dependent on the existence of a muscle-specific enhancer located from -2096 to -1743. The distal half of the enhancer, containing a pair of E-boxes, E1 and E2, was found to be a MyoD specific enhancer. In contrast, the activation by myogenin was dependent on the existence of the proximal half of the enhancer, containing three E-boxes, E3,E4,E5. In their E-boxes, the proximal E-box, E5 was essential for trans-activation by myogenin. Although MyoD and myogenin bound to E5 with similar affinity to each other, E5 and its falnking sequence worked as a myogenin-specific enhancer. From the analysis of the effect of chimeric proteins of MyoD and myogenin, the region(s) outside of the basic-helix-loop-helix (b-HLH) domain of myogenin was involved in the specificity of the myogenin-specific enhancer.
2) To understand regulatory mechanisms which govern transcriptional activation of the myogenin gene, transgenic mice bearing the lacZ gene driven by the upstream region of the myogenin gene were generated. Stereoscopic visualization of LacZ positive cells of these transgenic mouse embryos revealed that the upstream region of the myogenin gene conferred its transcriptional activation in cells of the skeletal muscle lineages in somites, limb buds, and viceral arches.
3) To investigate the molecular function of myogenin gene during muscle development, myogenin gene was desrurpted by homologous recombination. The analysis of effects of myogenin gene knock out is now in progress.

Report

(4 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • 1990 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Atsuko-Fujisawa-Sehara,Yoko Nabeshima,Toko Hosoda,Takeshi Obimata & Yoichi Nabeshima: "Myogenin Cortains Two Domaevis Conseved among Myogenin Factors." J.Biol.Chem.265. 15219-15223 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Taichi Uetsuki,Yoko Nabeshima,Atsuko Fujisawa-Sehara,Yoichi Nabeshima: "Rogulation of the Chethen Emrayonic Myosin light-chain(L23)Gene:" Mol.Cell.Biol.10. 2562-2569 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kazunori Hanaoka,Michido Hayasaka,Taichi Uetsuki,Yoichi Nabeshima: "A Etakle cellular marker for the analysis of mouse chimeras the bacterirl chloramphenisol aeetyltranslerare gene driven by for human elungotion factor 1α pronoter" Differentiation. 48. 183-189 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yoichi Nabeshima,Taichi Ueshuki,Tohru Komeya,Toko Nabeshima,Atsuko Fujisawa: "Transcriptional regulation of chickon myosinalkali lightchain genes." Frontiers in Muscle Reseach. 125-137 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yoichi Nabeshima,Taichi Uetsuki,Toko Nabeshima,Atsuko Fujisawa-Sehara: "Developnental Regnlatin of the chicken Alkali Light-Chain Exprlosion" Nouromuseular Perelopment and Disease. 145-155 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Atsuko Fujisawa-Sehara,Yoko Nabeshima,Tohru Komiya,Yoichi Nabeshima: "Differential trans-activation of Muscle-speatic Regulatary elements including myosin light chain box by chicken MyoD,Myogenin and FKF4" J.Biol.Cham.267. 10031-10038 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 鈴木 厚,吉田 幹晴,山本 秀子,小沢 えい二郎: "Glycoprotein-binding site of dystrophin is confined to the cysteine-rich domain and the first half of the carboxy-terminal domain" FEBS letters. 308. 154-160 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 吉田 幹晴,鈴木 厚,清水 輝夫,小沢 えい三郎: "Proteinase-sensitive sites on isolated rabbit dystrophin" Journal of Biochemistry. 112. 433-439 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 増田 俊和,藤巻 昇,小沢 えい二郎,石川 春律: "Confocal laser microscopy of dystrophin localization in guinea skeletal muscle fibers" Journal of Cell Biology. 119. 543-548 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 水野 裕司,埜中 征哉,平井 俊策,小沢 えい二郎: "Reciprocal expression of dystrophin and dystrophin-related protein(DRP)in muscles of Duchenne muscular dystrophy patients female DMD-carriers and control subjects" Journal of the Neurological Sciences.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 山本 秀子,萩原 康子,水野 裕司,吉田 幹晴,小沢 えい二郎: "Heterogenity of dystrophin associated proteins in miscles from patients with Duchenne muscular dystrophy"

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 水野 裕司,吉田 幹晴,埜中 征哉,平井 俊策,小沢 えい二郎: "Expression of utrophin(dystrophin relayed protein)and dystrophin-associated glycoproteins in muscles from patients with Duchenne muscular dystrophy"

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 鍋島 陽一: "新筋肉病学" 南江堂,

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Atsuko Fujisawa-Sehara, Kazunori Hanaoka, Michiko Hayasaka, Takako Hiromasa-Yagami, and Yo-ichi Nabeshima: "Upstream region of the myogenin gene confers transcriptional activation in muscle cell lineages during mouse embryogenesis." Biochem. Biophy. Res. Comm.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Atsuko Fujisawa-Sehara, Yoko Nabeshima, Yoko Hosida, Tohru Komiya, and Yo-ichi Nabeshima: "Differential transactivation of muscle-specific regulatory elements including myosin light chain box by chicken MyoD, Myogenin, and MRF4" J. Biol. Chem. 267. 10031-10038 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yo-ichi Nabeshima, Taichi Uetsuki, Yoko Nabeshima, Atsuko Fujisawa-Sehara: "Developmental regulation of the chicken myosin alkali light chain gene expression" Neuromuscular Development and Fisease. 145-155 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yo-ichi Nabeshima, Taichi Uetsuki, Tohru Komiya, Yoko Nabeshima, and Atsuko Fujisawa-Sehara: "Transcriptional regulation of chicken myosin alkali light chain gene" Frontiers of Muscle Research. 125-137 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kazunori Hanaoka, Michiko Hayasaka, Taichi Uetsuki, and Yo-ichi Nabeshima: "A stable cellular marker for the analysis of mouse chimeras: the bacterial chloramphenicol acetyltransferase gene driven by the human elongation factor 1 alpha promoter." Differentiation. 48. 183-189 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Taichi Uetsuki, Yoko Nabeshima, Atsuko Fujisawa-Sehara, and Yo-ichi Nabeshima: "Regulation of chicken embryonic myosin light chain (L23) gene." Mol. Cell. Biol.10. 2562-2568 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Atsuko Fujisawa-Sehara, Yoko Nabeshima, Yoko Hosoda, Takashi Obinata, and Yo-ichi Nabeshima: "Myogenin contains two domains conserved among myogenic factors" J. Biol. Chem. 265. 15219-15223 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] A.Fujisawa,K.Hanaoka,M.Hayasaka,T.Yagami and Y.Kabeshima: "Upstream region of the myogenin gene confers transeriptinal activation in muscle all lenearge during mouse enbryo genesis." Biochem,Biophys Res Comm.

    • Related Report
      1992 Annual Research Report
  • [Publications] A.Fujisawa,Y.Nabeshima,Y.Hosoda,T.Komiya,Y.Nabeshima: "Differential transactivation of nuscle specific regulatorgy elements including myosin eight chain box by myid myogeneri and MRF4" J.Biol.Chem.267. 10031-10038 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Fujisawa-Sehara A.;Nabeshima Y.et al.: "Differential Trans-activation of muscle-speuific regulatory elements in cluding is MLC box by chicken MyoD,Myogenin and MRF4" J.Biol.Chem.

    • Related Report
      1991 Annual Research Report
  • [Publications] Hanaoka K.;Nabeshima Y.et al.: "A stable ccllular marker for the analysis of mouse chimera:the bacterial chloramphenical a cctyltrans fer are gene driven by human slongate in facter I alpha promoter" Differentiation.

    • Related Report
      1991 Annual Research Report
  • [Publications] Matsuzaki F.;Nabeshima Y.et al: "Cloning of the Drosophila Prospero gene and its exprossion in ganglion mother cells" Biocham.Biopys.Res.Comm.

    • Related Report
      1991 Annual Research Report
  • [Publications] Taichi Uetsuki: "Regulation of the chieken embryonic myuiln lightーchain(L23)gene:Existence of a common regulatory element shared by myosin alkaliーchain genes." Mol.Coll.Biol.10. 2562-2567 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Atsuko FujisawaーSehara: "Myogenin contains two dumains conseved among myogemic factors." J.Biol.Chem. 265. 15219-15223 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 植日 太一: "筋発生・分化における遺伝子発現" 蛋白質・核酸・酵素. 35. 37-48 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 鍋島 陽一: "Id遺伝子…HLHファミリ-のNegative Regulator" 実験医学. 8. 79-84 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 鍋島 陽一: "筋細胞の分化を制御する遺伝子" 神経科学レビュ-5.

    • Related Report
      1990 Annual Research Report
  • [Publications] 鍋島 陽一: "筋分化制御遺伝子の機能と遺伝子発現" 代謝.

    • Related Report
      1990 Annual Research Report
  • [Publications] Yoーichi Nabeshima: "The Dynamic Sate of Musche Fibers(Regulatory elements in volved in chicken myosin alkrli light cherin gene expression)" Walter de Gruyter.Berlin・New York Editor Dirk Pette, (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Yoーichi Nabeshima: "Frontiers of Muscle Reseach(Transcriptional regulation of chicken myoshn alkaliーlight chrin gene)" Elsevier.Editor Eiziro Ozawa, (1991)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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