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MyoD: A Regulatory Gene of Skeletal Myogenesis

  • Stephen J. Tapscott
  • Robert L. Davis
  • Andrew B. Lassar
  • Harold Weintraub
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 280)

Abstract

MyoD is expressed only in skeletal muscle (1), and could be considered a master regulatory gene of myogenesis. When expressed in non-muscle cells, MyoD converts those cells to myoblasts (2). Specifically, the mouse fibroblast cell line 10T1/2 does not express either MyoD or any of several muscle specific genes. Forced expression of MyoD in l0Tl/2 cells converts this cell to a myoblast: In growth medium the cell divides and expresses MyoD and other muscle lineage markers, but does not express myosin, desmin, or other markers of muscle terminal differentiation; in differentiation medium the cell withdraws from the cell cycle and initiates expression of desmin, myosin and other proteins of terminal differentiation (1). In addition to activating muscle structural genes, MyoD also positively regulates its own transcription, as well as myogenin, a related muscle regulatory protein (3). This positive autoregulatory circuit could be a mechanism for amplifying expression of muscle regulatory genes and might serve to maintain expression of these genes once a cell has become committed to the myoblast lineage.

Keywords

Muscular Dystrophy Myosin Heavy Chain Mouse Fibroblast Cell Line Master Regulatory Gene MyoD Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    R.D. Davis, H. Weintraub and A.B. Lassar. 1987. Expression of a single transfected cDNA converts fibroblasts to myoblasts (1987).Cell, 51: 987–1000.PubMedCrossRefGoogle Scholar
  2. 2.
    H. Weintraub et al. 1989. Activation of muscle specific genes in pigment, nerve, fat, liver and fibroblast cell lines by forced expression of MyoD. PNAS, 86: 5434–5438.PubMedCrossRefGoogle Scholar
  3. 3.
    M.J. Thayer et al. 1989. Positive autoregulation of the myogenic determination gene MyoDi. Cell, 58: 241–248.PubMedCrossRefGoogle Scholar
  4. 4.
    S.J. Tapscott et al. 1988. MyoDi: a nuclear phosphoprotein requiring a myc homology region to convert fibroblasts to myoblasts. Science, 242: 405–411.PubMedCrossRefGoogle Scholar
  5. 5.
    F.W. Alt, R.A. DePinho, K. Zimmerman, E. Legouy, K. Hutton, P. Ferrier, A. Tesfaye, G.D. Yoncopoulos and P. Nisen 1986. The human myc-gene family. Cold Spring Harbor Symp. Quant. Biol., 51: 931–941.Google Scholar
  6. 6.
    C. Murre, P.S. McCaw and D. Baltimore. 1989. A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins. Cell, 56: 777–783PubMedCrossRefGoogle Scholar
  7. 7.
    W.E. Wright, D.A. Sassoon and V.K. Lin. 1989. Myogenin, a factor regulating myogenesis has a domain homologous to MyoD. Cell, 56: 607–617.PubMedCrossRefGoogle Scholar
  8. 8.
    T. Braun, G. Buschhausen-Denker, E. Bober and H.H. Arnold. 1989. A novel human muscle factor related to but distinct from MyoDi induces myogenic conversion in 10T1/2 fibroblasts. EMBO J, 8: 701–709.Google Scholar
  9. 9.
    M. Caudy et al. 1988. Daughterless, a drosophila gene essential for both neurogenesis and sex determination, has sequence similarities to myc and the achaete-scute complex. Cell, 55: 1061–1067.PubMedCrossRefGoogle Scholar
  10. 10.
    R. Villares and C.V. Cabrera. 1987. The achaete-scute gene complex of D. melanogaster: conserved domains in a subset of genes required for neurogenesis and their homology to myc. Cell, 50: 415–424.PubMedCrossRefGoogle Scholar
  11. 11.
    A.B. Lassar et al. 1989. MyoD is a sequence specific binding protein requiring a region of myc homology to bind to the muscle creatine kinase enhancer. Cell, 58: 823–831.PubMedCrossRefGoogle Scholar
  12. 12.
    C. Murre et al. 1989. Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence. Cell, 58: 537–544.PubMedCrossRefGoogle Scholar
  13. 13.
    R.L. Davis, P.-F. Cheng, A.B. Lassar and H. Weintraub. 1990. The MyoD DNA binding domain contains a recognition code for muscle-specific gene activation. Cell, 60: 733–746.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Stephen J. Tapscott
    • 1
  • Robert L. Davis
    • 1
  • Andrew B. Lassar
    • 1
  • Harold Weintraub
    • 1
  1. 1.Fred Hutchinson Cancer Research CenterSeattleUSA

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