MYF6 explained

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]

Further reading

• Braun T, Arnold HH . 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 . October 1991 . 1945842 . 328970 . 10.1093/nar/19.20.5645 .
• Langlands K, Yin X, Anand G, Prochownik EV . Differential interactions of Id proteins with basic-helix-loop-helix transcription factors . The Journal of Biological Chemistry . 272 . 32 . 19785–19793 . August 1997 . 9242638 . 10.1074/jbc.272.32.19785 . free .
• Kong Y, Flick MJ, Kudla AJ, Konieczny SF . Muscle LIM protein promotes myogenesis by enhancing the activity of MyoD . Molecular and Cellular Biology . 17 . 8 . 4750–4760 . August 1997 . 9234731 . 232327 . 10.1128/mcb.17.8.4750 .
• Onions J, Hermann S, Grundström T . A novel type of calmodulin interaction in the inhibition of basic helix-loop-helix transcription factors . Biochemistry . 39 . 15 . 4366–4374 . April 2000 . 10757985 . 10.1021/bi992533u .
• Cupelli L, Renault B, Leblanc-Straceski J, Banks A, Ward D, Kucherlapati RS, Krauter K . 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 . 1996 . 8978788 . 10.1159/000134201 .
• Kosek DJ, Kim JS, Petrella JK, Cross JM, Bamman MM . 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 . August 2006 . 16614355 . 10.1152/japplphysiol.01474.2005 .
• Black BL, Molkentin JD, Olson EN . 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 . January 1998 . 9418854 . 121453 . 10.1128/mcb.18.1.69 .
• 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 . The EMBO Journal . 9 . 3 . 821–831 . March 1990 . 2311584 . 551742 . 10.1002/j.1460-2075.1990.tb08179.x .
• Kerst B, Mennerich D, Schuelke M, Stoltenburg-Didinger G, von Moers A, Gossrau R, van Landeghem FK, Speer A, Braun T, Hübner C . Heterozygous myogenic factor 6 mutation associated with myopathy and severe course of Becker muscular dystrophy . Neuromuscular Disorders . 10 . 8 . 572–577 . December 2000 . 11053684 . 10.1016/S0960-8966(00)00150-4 . 29535555 .

Notes and References

1. Web site: Entrez Gene: Myogenic factor 6 (herculin) . 2013-08-19 .
2. 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 . The EMBO Journal . 9 . 3 . 821–831 . March 1990 . 2311584 . 551742 . 10.1002/j.1460-2075.1990.tb08179.x .
3. Cupelli L, Renault B, Leblanc-Straceski J, Banks A, Ward D, Kucherlapati RS, Krauter K . 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 . 1996 . 8978788 . 10.1159/000134201 .
4. Kassar-Duchossoy L, Gayraud-Morel B, Gomès D, Rocancourt D, Buckingham M, Shinin V, Tajbakhsh S . Mrf4 determines skeletal muscle identity in Myf5:Myod double-mutant mice . Nature . 431 . 7007 . 466–471 . September 2004 . 15386014 . 10.1038/nature02876 . 4413512 . 2004Natur.431..466K .
5. Moretti I, Ciciliot S, Dyar KA, Abraham R, Murgia M, Agatea L, Akimoto T, Bicciato S, Forcato M, Pierre P, Uhlenhaut NH, Rigby PW, Carvajal JJ, Blaauw B, Calabria E, Schiaffino S . MRF4 negatively regulates adult skeletal muscle growth by repressing MEF2 activity . Nature Communications . 7 . 12397 . August 2016 . 27484840 . 4976255 . 10.1038/ncomms12397 .
6. Arnold HH, Braun T . Targeted inactivation of myogenic factor genes reveals their role during mouse myogenesis: a review . The International Journal of Developmental Biology . 40 . 1 . 345–353 . February 1996 . 8735947 .
7. Hinits Y, Osborn DP, Carvajal JJ, Rigby PW, Hughes SM . Mrf4 (myf6) is dynamically expressed in differentiated zebrafish skeletal muscle . Gene Expression Patterns . 7 . 7 . 738–745 . August 2007 . 17638597 . 3001336 . 10.1016/j.modgep.2007.06.003 .
8. Kerst B, Mennerich D, Schuelke M, Stoltenburg-Didinger G, von Moers A, Gossrau R, van Landeghem FK, Speer A, Braun T, Hübner C . Heterozygous myogenic factor 6 mutation associated with myopathy and severe course of Becker muscular dystrophy . Neuromuscular Disorders . 10 . 8 . 572–577 . December 2000 . 11053684 . 10.1016/S0960-8966(00)00150-4 . 29535555 .