Biology:MYF6
 Generic protein structure example |
Myogenic factor 6 (also known as Mrf4 or herculin) is a protein that in humans is encoded by the MYF6 gene.
[1]
This gene is also known in the biomedical literature as MRF4 and herculin. MYF6 is a myogenic regulatory factor (MRF) involved in the process known as myogenesis.[2][3]
Function
MYF6/Mrf4 is a member of the myogenic factor (MRF) family of transcription factors that regulate skeletal muscle myogenesis and muscle regeneration. Myogenic factors are basic helix-loop-helix (bHLH) transcription factors. MYF6 is a gene that encodes a protein involved in the regulation of myogenesis. The precise role(s) of Myf6/Mrf4 in myogenesis are unclear, although in mice it is able to initiate myogenesis in the absence of Myf5 and MyoD, two other MRFs.[4] The portion of the protein integral to myogenesis regulation requires the basic helix-loop-helix (bHLH) domain that is conserved among all of the genes in the MRF family.
MYF6 is expressed exclusively in skeletal muscle, and it is expressed at a higher levels in adult skeletal muscle than all of the other MRF family genes. In mouse, Myf6/Mrf4 differs somewhat from the other MRF genes due to its two-phase expression. Initially, Myf6 is transiently expressed along with Myf-5 in the somites during the early stages of myogenesis. However, it is more noticeably expressed postnatally. This suggests that it serves an important role in the maintenance and repair of adult skeletal muscle.[5]
The MYF6 gene is physically linked to the MYF5 gene on chromosome 12, and similar linkage is observed in all vertebrates. Mutations in the mouse Myf6 gene typically exhibit reduced levels of Myf5.[6] Despite reductions in muscle mass of the back and defective rib formation, Myf6 mutants still exhibit fairly normal skeletal muscle. This demonstrates that Myf6 is not essential for the formation of most myofibers, at least in the strains of mice tested.
In zebrafish, Myf6/Mrf4 is expressed in all terminally differentiated muscle examined, but expression has not been reported in muscle precursor cells.[7]
Clinical significance
Mutations in the MYF6 gene are associated with autosomal dominant centronuclear myopathy (ADCNM) and Becker's muscular dystrophy.[8]
References
- ↑ "Entrez Gene: Myogenic factor 6 (herculin)". https://www.ncbi.nlm.nih.gov/gene/4618.
- ↑ "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 (3): 821–31. March 1990. doi:10.1002/j.1460-2075.1990.tb08179.x. PMID 2311584.
- ↑ "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". Cytogenet. Cell Genet. 72 (2–3): 250–1. 1996. doi:10.1159/000134201. PMID 8978788.
- ↑ "Mrf4 determines skeletal muscle identity in Myf5:Myod double-mutant mice". Nature 431 (7007): 466–71. 2004. doi:10.1038/nature02876. PMID 15386014. Bibcode: 2004Natur.431..466K.
- ↑ Moretti, I. et al. MRF4 negatively regulates adult skeletal muscle growth by repressing MEF2 activity. Nat. Commun. 7:12397 doi: 10.1038/ncomms12397 (2016).
- ↑ Arnold, H. H.; Braun, T. (1996-02-01). "Targeted inactivation of myogenic factor genes reveals their role during mouse myogenesis: a review". The International Journal of Developmental Biology 40 (1): 345–353. ISSN 0214-6282. PMID 8735947.
- ↑ "Mrf4 (myf6) is dynamically expressed in differentiated zebrafish skeletal muscle". Gene Expr Patterns 7 (7): 738–745. 2007. doi:10.1016/j.modgep.2007.06.003. PMID 17638597.
- ↑ "Heterozygous myogenic factor 6 mutation associated with myopathy and severe course of Becker muscular dystrophy". Neuromuscul. Disord. 10 (8): 572–7. December 2000. doi:10.1016/S0960-8966(00)00150-4. PMID 11053684.
Further reading
- Braun, T.; Arnold, H. H. (1991). "The four human muscle regulatory helix-loop-helix proteins Myf3-Myf6 exhibit similar hetero-dimerization and DNA binding properties". Nucleic Acids Research 19 (20): 5645–5651. doi:10.1093/nar/19.20.5645. PMID 1945842.
- Langlands, K.; Yin, X.; Anand, G.; Prochownik, E. V. (1997). "Differential interactions of Id proteins with basic-helix-loop-helix transcription factors". The Journal of Biological Chemistry 272 (32): 19785–19793. doi:10.1074/jbc.272.32.19785. PMID 9242638.
- Kong, Y.; Flick, M. J.; Kudla, A. J.; Konieczny, S. F. (1997). "Muscle LIM protein promotes myogenesis by enhancing the activity of MyoD". Molecular and Cellular Biology 17 (8): 4750–4760. doi:10.1128/mcb.17.8.4750. PMID 9234731.
- Onions, J.; Hermann, S.; Grundström, T. (2000). "A novel type of calmodulin interaction in the inhibition of basic helix-loop-helix transcription factors". Biochemistry 39 (15): 4366–4374. doi:10.1021/bi992533u. PMID 10757985.
- Cupelli, L.; Renault, B.; Leblanc-Straceski, J.; Banks, A.; Ward, D.; Kucherlapati, R. S.; Krauter, K. (1996). "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". Cytogenetics and Cell Genetics 72 (2–3): 250–251. doi:10.1159/000134201. PMID 8978788.
- Kosek, D. J.; Kim, J. S.; Petrella, J. K.; Cross, J. M.; Bamman, M. M. (2006). "Efficacy of 3 days/wk resistance training on myofiber hypertrophy and myogenic mechanisms in young vs. Older adults". Journal of Applied Physiology 101 (2): 531–544. doi:10.1152/japplphysiol.01474.2005. PMID 16614355.
- Black, B. L.; Molkentin, J. D.; Olson, E. N. (1998). "Multiple roles for the MyoD basic region in transmission of transcriptional activation signals and interaction with MEF2". Molecular and Cellular Biology 18 (1): 69–77. doi:10.1128/mcb.18.1.69. PMID 9418854.
- Braun, T.; Bober, E.; Winter, B.; Rosenthal, N.; Arnold, H. H. (1990). "Myf-6, a new member of the human gene family of myogenic determination factors: Evidence for a gene cluster on chromosome 12". The EMBO Journal 9 (3): 821–831. doi:10.1002/j.1460-2075.1990.tb08179.x. PMID 2311584.
- Kerst, B.; Mennerich, D.; Schuelke, M.; Stoltenburg-Didinger, G.; Von Moers, A.; Gossrau, R.; Van Landeghem, F. K.; Speer, A. et al. (2000). "Heterozygous myogenic factor 6 mutation associated with myopathy and severe course of Becker muscular dystrophy". Neuromuscular Disorders 10 (8): 572–577. doi:10.1016/S0960-8966(00)00150-4. PMID 11053684.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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