Abstract
Insight into the molecular mechanisms that control establishment of the skeletal muscle phenotype has recently been obtained through cloning of a family of muscle-specific regulatory factors that can activate myogenesis when transfected into non-muscle cells. This family of factors, which includes MyoD, myogenin, myf-5, and MRF4, can bind DNA and transactivate muscle-specific genes in collaboration with ubiquitous cellular factors. Growth factors play an antagonistic role in myogenesis by suppressing the actions of the myogenic regulatory factor family. This review will focus on the regulation and mechanism of action of this family of myogenic regulatory factors and on the central role of peptide growth factors in modulating their expression and biological activities.
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Spizz G, Roman D, Strauss A, Olson EN: Serum and fibroblast growth factor inhibit myogenic differentiation through a mechanism dependent on protein synthesis and independent of cell proliferation. J Biol Chem 261: 9483–9488, 1986
Olson EN, Sternberg E, Hu JS, Spizz G, Wilcox C: Regulation of myogenic differentiation by type beta transforming growth factor. J Cell Biol 103: 1799–1805, 1986
Clegg CH, Linkhart TA, Olwin BB, Hauschka SD: Growth factor control of skeletal muscle differentiation occurs in Gl-phase and is repressed by fibroblast growth factor. J Cell Biol 105: 949–956, 1987
Davis RL, Weintraub H, Lassar AB: Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell 51: 987–1000, 1987
Weintraub H, Tapscott SJ, Davis RL, Thayer MJ, Adam MA, Lassar AB, Miller AD: Activation of muscle specific genes in pigment, nerve, fat, liver and fibroblast cell lines by forced expression of MyoD. Proc Natl Acad Sci 86: 5434–5438, 1989
Schafer BW, Blakely BT, Darlington GJ, Blau HM: Effect of cell history on response to helix-loop-helix family of myogenic regulators. Nature 344: 454–458, 1990
Wright WE, Sassoon DA, Lin VK: Myogenin, a factor regulating myogenesis, has a domain homologous to MyoD1. Cell 56: 607–617, 1989
Edmondson DG, Olson EN: A gene with homology to the myc similarity region of MyoD1 is expressed during myogenesis and is sufficient to activate the muscle differentiation program. Genes Dev 3: 628–640, 1989
Braun T, Buschhausen-Denker G, Bober E, Tannich E, Arnold HH: A novel human muscle factor related to but distinct from MyoD1 induces myogenic conversion in 10T1/2 fibroblasts. EMBO J 8: 701–709, 1989
Rhodes SJ, Konieczny SF: Identification of MRF4: A new member of the muscle regulatory factor gene family. Genes Dev 3: 2050–2061, 1989
Miner JH, Wold B: Herculin, a fourth member of the MyoD family of myogenic regulatory genes. Proc Natl Acad Sci USA 87: 1089–1093, 1990
Braun T, Bober E, Winter B, Rosenthal N, Arnold HH: Myf-6, a new member of the human gene family of myogenic determination factors: evidence for a gene cluster on chromosome 12. EMBO J 9: 821–831, 1990
Murre C, McCaw PS, Baltimore D: A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins. Cell 56: 777–783, 1989a
Murre C, McCaw PS, Vaessin H, Candy M, Jan LY, Jan YN, Cabrera CV, Buskin JN, Hauschka SD, Lassar AB, Weintraub H, Baltimore D: Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence. Cell 58: 537–544, 1989b
Davis RL, Cheng P-F, Lassar AB, Weintraub H: The MyoD DNA binding domain contains a recognition code for muscle-specific gene activation. Cell 60: 733–746, 1990
Tapscott SJ, Davis RL, Thayer MJ, Cheng P-F, Weintraub H, Lassar AB: MyoD1: A nuclear phosphoprotein requiring a myc homology region to convert fibroblasts by myoblasts. Science 242: 405–411, 1988
Brennan TJ, Olson EN: Myogenin resides in the nucleus and acquires high affinity for a conserved enhancer element on heterodimerization. Genes Dev 4: 582–595, 1990
Buskin JN, Hauschka SD: Identification of a myocyt-especific nuclear factor which binds to the muscle-specific enhancer of the mouse muscle creatine kinase gene. Mol Cell Biol 9: 2627–2640, 1989
Lassar AB, Buskin JN, Lockshon D, Davis RL, Apone S, Hauschka SD, Weintraub H: MyoD is a sequence-specific DNA binding protein requiring a region of myc homology to bind to the muscle creative kinase enhancer. Cell 58: 823–831, 1989a
Beckmann H, Su L-K, Kadesch T: TFE3: A helix-loophelix protein that activates transcription through the immunoglobulin enhancer µE3 motif. Genes Dev 4: 167–179, 1990
Piette J, Bessereau J-L, Huchet M, Changeux J-P: Two adjacent MyoD1-binding sites regulate expression of the acetylcholine receptor a-subunit gene. Nature 345: 353–355, 1990
Gossett L, Kelvin D, Sternberg E, Olson EN: A new myocyte-specific enhancer binding factor that recognizes a conserved element associated with multiple muscle-specific genes. Mol Cell Biol 9: 5022–5033, 1989
Mar JH, Ordahl CP: M-CAT binding factor, a novel transacting factor governing muscle-specific transcription. Mol Cell Biol, in press, 1990
Vaidya TB, Rhodes SJ, Taparowsky EJ, Konieczny SF: Fibroblast growth factor and transforming growth factor β repress transcription of the myogenic regulatory gene MyoD1. Mol Cell Biol 9: 3576–3579, 1989
Benezra R, Davis RL, Lockshon D, Turner DL, Weintraub H: The protein Id: a negative regulator of helix-loop-helix DNA binding proteins. Cell 61: 49–59, 1990
Olson EN, Spizz G, Tainsky MA: The oncogenic form of N-ras prevents skeletal myoblast differentiation. Mol Cell Biol 7: 2104–2111, 1987
Gossett LA, Zhang W, Olson EN: Dexamethasone-dependent inhibition of differentiation of C2 myoblasts bearing steroid-inducible N-ras oncogenes. J Cell Biol 106: 2127–2137, 1988
Brennan T, Chakraborty T, Olson EN: TGFB inhibits the actions of myogenin through a mechanism independent of DNA binding. Roc Natl Acad Sci USA, in press, 1991.
Thayer MJ, Tapscott SJ, Davis RL, Wright WE, Lassar AB, Weintraub H: Positive autoregulation of the myogenic determination gene MyoD1. Cell 58: 241–248, 1989
Braun T, Bober E, Buschhausen-Denker G, Kotz S, Grzeschik K, Arnold HH: Differential expression of myogenic determination genes in muscle cells: possible autoactivation by the Myf gene products. EMBO J 8: 3617–3625; 1989b
Sorrentino V, Pepperkok R, Davis RL, Ansorge W, Philipson L: Cell proliferation inhibited by MyoD1 independently of myogenic differentiation. Nature 345: 813–815, 1990
Lassar AB, Thayer MJ, Overell RW, Weintraub H: Transformation by activated RAS or FOS prevents myogenesis by inhibiting expression of MyoD1. Cell 5: 659–667, 1989b
Falcone G, Tato F, Alema S: Distinctive effects of the viral oncogenes myc, erb, fps, and src on the differentiation program of quail myogenic cells. Proc Natl Acad Sci 82: 426–430, 1985
Schneider MD, Perryman MB, Payne PA, Spizz G, Roberts R, Olson EN: Autonomous expression of c-myc in BC3H1 cells partially inhibits but does not prevent myogenic differentiation. Mol Cell Biol 7: 1973–1977, 1987
LaRocca SA, Grossi M, Falcone G, Alema S, Tato F: Interaction with normal cells suppresses the transformed phenotype of v-myc transformed quail muscle cells. Cell 58: 123–131, 1989
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Olson, E.N., Brennan, T.J., Chakraborty, T. et al. Molecular control of myogenesis: antagonism between growth and differentiation. Mol Cell Biochem 104, 7–13 (1991). https://doi.org/10.1007/BF00229797
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DOI: https://doi.org/10.1007/BF00229797