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Gene Review

MYF5  -  myogenic factor 5

Homo sapiens

Synonyms: BHLHC2, Class C basic helix-loop-helix protein 2, Myf-5, Myogenic factor 5, bHLHc2
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Disease relevance of MYF5

  • Rhabdomyosarcoma (RMS) has deregulated proliferation and is blocked in the differentiation program despite Myf-5, MyoD and myogenin expression [1].
  • Two recombinant baculoviruses BcV-myf4 and BcV-myf5 have been constructed to synthesize the human myogenic determination factors myogenin (myf4) and myf5 in eucaryotic cells [2].

High impact information on MYF5

  • In epaxial, hypaxial, limb, and head muscle progenitors, Myf5 is controlled by lineage-specific transcription enhancers, providing evidence that multiple mechanisms control progenitor specification at different sites of myogenesis in the embryo [3].
  • Developmental signaling ligands and their signal transduction effectors function both interactively and independently to control Myf5 and MyoD activation in muscle progenitor lineages, likely through direct regulation of their transcription enhancers [3].
  • Here we report that myf5 contains an intrinsic transcriptional activation domain which is distinct from the helix-loop-helix motif [4].
  • To investigate the potential of myf5 as a transcription factor, we have fused the GAL4 DNA-binding domain to various parts of the myf5 protein and analysed the transactivation of a GAL4 reporter plasmid [4].
  • We conclude that Pax3 directly regulates Myf5 in the hypaxial somite and its derivatives [5].

Biological context of MYF5


Anatomical context of MYF5

  • PURPOSE: This study examined 12 wk of creatine (Cr) supplementation and heavy resistance training on skeletal muscle creatine kinase (M-CK) mRNA expression and the mRNA and protein expression of the myogenic regulatory factors Myo-D, myogenin, MFR-4, and Myf5 [10].
  • In addition, an isokinetic dynamometer was used to measure maximal knee-extension power (Wmax), and needle biopsy samples taken from the vastus lateralis muscle were examined to asses expression of the myogenic transcription factors MyoD, myogenin, Myf5, and MRF4, and muscle fibre diameters [11].
  • Myf-5 and MyoD are more homologous to one another than to the others, are expressed in myoblasts before differentiation, and are required for the determination or survival of muscle progenitor cells [12].
  • Injected cells also localized under the basal lamina of host muscle fibers and expressed satellite cell markers such as M-cadherin and MYF5 [13].
  • We have characterized a 145-base-pair (bp) regulatory element, at -57.5 kb from Myf5, that directs transgene expression to the mature somite, notably to myogenic cells of the hypaxial domain that form ventral trunk and limb muscles [5].

Associations of MYF5 with chemical compounds

  • Normal activity can be restored by replacing the serine residues with glutamate suggesting that a negative charge at these sites is obligatory for Myf-5 activity [14].
  • We have obtained partial sequences for MyoD, myogenin, and myf5 from Torpedo californica and have measured their mRNAs in several organs, using ribonuclease protection [15].
  • Several molecules have been implicated in the regulation of satellite cell quiescence, activation and renewal, including the transcription factors Pax7, MyoD and Myf5, the cell-surface glycoprotein CD34, and the membrane lipid sphingomyelin [16].
  • Conversely, mutation of a serine residue (S158) stabilizes Myf5 in nonsynchronized cultures but not at mitosis [17].
  • In the myogenic cell line C2, we have found that Myf5 expression, unlike that of MyoD, is restricted to cycling cells and regulated by proteolysis at mitosis [17].

Regulatory relationships of MYF5

  • Myogenic 10T1/2 cells, however, induced by the expression of either pEMSV-Myf-4 or pEMSV-Myf-5 activate their endogenous mouse Myf-6 gene [9].
  • Furthermore, we show that the BMP antagonist Noggin is expressed within the dorsomedial lip of the dermomyotome, where Pax3-expressing cells first initiate the expression of MyoD and Myf5 to give rise to myotomal cells in the medial somite [18].
  • Canonical Wnt/beta-catenin signaling regulates the activation of the myogenic determination gene Myf5 at the onset of myogenesis, but the underlying molecular mechanism is unknown [19].
  • In cells which stably express E1a, myogenin expression is completely suppressed while Myf-5 continues to be synthesized normally [20].
  • Myf-5 is later expressed in the presegmented mesoderm (psm) in a reiterating pattern that is coordinated with somitogenesis and also colocalizes with the Notch ligand C-Delta-1 [21].

Other interactions of MYF5

  • MyoD and MRF4 expression was not altered under either condition and no myf5 expression was detected [22].
  • A 2.0 kb myf3 transcript was observed in 85% of tumours, a 1.8 kb myf4 transcript was detected in 70% of tumours and a 1.7 kb myf5 transcript was observed in 55% of tumours [23].
  • There were no differences in Myf5, CD36, and CPT1 mRNA levels 0-24 h post-RE [24].
  • In Xenopus, p38 signaling was shown to be needed for the early expression of Myf5 and for the expression of several muscle structural genes [25].
  • The cell population was identified using the satellite markers CD34, m-cadherin and Myf5, and the proliferative capacity of the adult stem cells was determined [26].

Analytical, diagnostic and therapeutic context of MYF5

  • We performed a comparative sequence analysis of the MYF5/MYF6 locus in swine, cattle, dog, chicken and zebrafish on the basis of structural and functional information from human and mouse [6].


  1. Muscle regulatory factor MRF4 activates differentiation in rhabdomyosarcoma RD cells through a positive-acting C-terminal protein domain. Sirri, V., Leibovitch, M.P., Leibovitch, S.A. Oncogene (2003) [Pubmed]
  2. Baculovirus-expressed myogenic determination factors require E12 complex formation for binding to the myosin-light-chain enhancer. Braun, T., Gearing, K., Wright, W.E., Arnold, H.H. Eur. J. Biochem. (1991) [Pubmed]
  3. Myogenic regulatory factors and the specification of muscle progenitors in vertebrate embryos. Pownall, M.E., Gustafsson, M.K., Emerson, C.P. Annu. Rev. Cell Dev. Biol. (2002) [Pubmed]
  4. Transcriptional activation domain of the muscle-specific gene-regulatory protein myf5. Braun, T., Winter, B., Bober, E., Arnold, H.H. Nature (1990) [Pubmed]
  5. A novel genetic hierarchy functions during hypaxial myogenesis: Pax3 directly activates Myf5 in muscle progenitor cells in the limb. Bajard, L., Relaix, F., Lagha, M., Rocancourt, D., Daubas, P., Buckingham, M.E. Genes Dev. (2006) [Pubmed]
  6. Identification and analysis of putative regulatory sequences for the MYF5/MYF6 locus in different vertebrate species. Maak, S., Neumann, K., Swalve, H.H. Gene (2006) [Pubmed]
  7. Chromosomal assignment of six muscle-specific genes in cattle. Ryan, A.M., Schelling, C.P., Womack, J.E., Gallagher, D.S. Anim. Genet. (1997) [Pubmed]
  8. Assignment of the human myogenic factors 5 and 6 (MYF5, MYF6) gene cluster to 12q21 by in situ hybridization and physical mapping of the locus between D12S350 and D12S106. Cupelli, L., Renault, B., Leblanc-Straceski, J., Banks, A., Ward, D., Kucherlapati, R.S., Krauter, K. Cytogenet. Cell Genet. (1996) [Pubmed]
  9. Myf-6, a new member of the human gene family of myogenic determination factors: evidence for a gene cluster on chromosome 12. Braun, T., Bober, E., Winter, B., Rosenthal, N., Arnold, H.H. EMBO J. (1990) [Pubmed]
  10. Effects of oral creatine and resistance training on myogenic regulatory factor expression. Willoughby, D.S., Rosene, J.M. Medicine and science in sports and exercise. (2003) [Pubmed]
  11. Oral creatine supplementation facilitates the rehabilitation of disuse atrophy and alters the expression of muscle myogenic factors in humans. Hespel, P., Op't Eijnde, B., Van Leemputte, M., Ursø, B., Greenhaff, P.L., Labarque, V., Dymarkowski, S., Van Hecke, P., Richter, E.A. J. Physiol. (Lond.) (2001) [Pubmed]
  12. Determination versus differentiation and the MyoD family of transcription factors. Megeney, L.A., Rudnicki, M.A. Biochem. Cell Biol. (1995) [Pubmed]
  13. Human circulating AC133(+) stem cells restore dystrophin expression and ameliorate function in dystrophic skeletal muscle. Torrente, Y., Belicchi, M., Sampaolesi, M., Pisati, F., Meregalli, M., D'Antona, G., Tonlorenzi, R., Porretti, L., Gavina, M., Mamchaoui, K., Pellegrino, M.A., Furling, D., Mouly, V., Butler-Browne, G.S., Bottinelli, R., Cossu, G., Bresolin, N. J. Clin. Invest. (2004) [Pubmed]
  14. Two putative protein kinase CK2 phosphorylation sites are important for Myf-5 activity. Winter, B., Kautzner, I., Issinger, O.G., Arnold, H.H. Biol. Chem. (1997) [Pubmed]
  15. Expression of myogenic factors in skeletal muscle and electric organ of Torpedo californica. Neville, C.M., Schmidt, J. FEBS Lett. (1992) [Pubmed]
  16. Satellite cell self-renewal. Collins, C.A. Current opinion in pharmacology. (2006) [Pubmed]
  17. Constitutive instability of muscle regulatory factor Myf5 is distinct from its mitosis-specific disappearance, which requires a D-box-like motif overlapping the basic domain. Lindon, C., Albagli, O., Domeyne, P., Montarras, D., Pinset, C. Mol. Cell. Biol. (2000) [Pubmed]
  18. Regulation of dorsal somitic cell fates: BMPs and Noggin control the timing and pattern of myogenic regulator expression. Reshef, R., Maroto, M., Lassar, A.B. Genes Dev. (1998) [Pubmed]
  19. The Wnt/{beta}-catenin pathway regulates Gli-mediated Myf5 expression during somitogenesis. Borello, U., Berarducci, B., Murphy, P., Bajard, L., Buffa, V., Piccolo, S., Buckingham, M., Cossu, G. Development (2006) [Pubmed]
  20. Regulation of myogenin expression in normal and transformed myogenic cell lines. Arnold, H.H., Braun, T., Bober, E., Buchberger, A., Winter, B., Salminen, A. Symp. Soc. Exp. Biol. (1992) [Pubmed]
  21. Myf-5 is transiently expressed in nonmuscle mesoderm and exhibits dynamic regional changes within the presegmented mesoderm and somites I-IV. Kiefer, J.C., Hauschka, S.D. Dev. Biol. (2001) [Pubmed]
  22. cAMP effects on myogenic gene expression in rhabdomyosarcoma cells. Wasserman, L.M., Newsham, I., Huang, H.J., Cavenee, W.K. Exp. Cell Res. (1996) [Pubmed]
  23. Expression of members of the myf gene family in human rhabdomyosarcomas. Clark, J., Rocques, P.J., Braun, T., Bober, E., Arnold, H.H., Fisher, C., Fletcher, C., Brown, K., Gusterson, B.A., Carter, R.L. Br. J. Cancer (1991) [Pubmed]
  24. Time course of myogenic and metabolic gene expression in response to acute exercise in human skeletal muscle. Yang, Y., Creer, A., Jemiolo, B., Trappe, S. J. Appl. Physiol. (2005) [Pubmed]
  25. The p38 MAPK signaling pathway: a major regulator of skeletal muscle development. Keren, A., Tamir, Y., Bengal, E. Mol. Cell. Endocrinol. (2006) [Pubmed]
  26. Muscle-derived stem cells used to treat skin defects prevent wound contraction and expedite reepithelialization. Buján, J., Pascual, G., Corrales, C., Gómez-Gil, V., Garcia-Honduvilla, N., Bellón, J.M. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society. (2006) [Pubmed]
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