IIb or not IIb? Regulation of myosin heavy chain gene expression in mice and men
Open accessAbstract
Background: While the myosin heavy chain IIb isoform (MyHC-IIb) is the predominant motor protein in most skeletal muscles of rats and mice, the messenger RNA (mRNA) for this isoform is only expressed in a very small subset of specialized muscles in adult large mammals, including humans. Results: We identify the DNA sequences limiting MyHC-IIb expression in humans and explore the activation of this gene in human skeletal muscle. We demonstrate that the transcriptional activity of ~1.0 kb of the human MyHC-IIb promoter is greatly reduced compared to that of the corresponding mouse sequence in both mouse and human myotubes in vitro and show that nucleotide differences that eliminate binding sites for myocyte enhancer factor 2 (MEF2) and serum response factor (SRF) account for this difference. Despite these differences, we show that MyHC-IIb mRNA is expressed in fetal human muscle cells and that MyHC-IIb mRNA is significantly up-regulated in the skeletal muscle of Duchene muscular dystrophy patients. Conclusions: These data identify the genetic basis for a key phenotypic difference between the muscles of large and small mammals, and demonstrate that mRNA expression of the MyHC-IIb gene can be re-activated in human limb muscle undergoing profound degeneration/regeneration.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Human skeletal muscle does not express MyHC-IIb protein, at least in part due to reduced activity of the human MyHC-IIb promoter region.
“In contrast, human skeletal muscle does not express MyHC-IIb protein, a phenomenon that appears to be, at least in part, due to a reduction in the activity of the human MyHC-IIb promoter region (37).”
From Sex-Based Differences in Skeletal Muscle Kinetics and Fiber-Type Composition (2015) · cites this paper as [37]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Type IIx myosin heavy chain transcripts are expressed in type IIb fibers of human skeletal muscle
Smerdu, V., Karsch‐Mizrachi, I., Campione, M., Leinwand, L. A., & Schiaffino, S. (1994) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1994.267.6.c1723 · Cited by 456 · cited 1× · see citing works
“However, although MyHCIIb is highly expressed at both the messenger RNA (mRNA) and protein level in murine skeletal muscle, evidence to date suggests that this isoform is effectively only expressed at the mRNA level in a very small subset of specialized muscles in the adult human [5-10].”
BackgroundSelf-citationGorza, L. (1990) · Journal of Histochemistry & Cytochemistry · doi:10.1177/38.2.2137154 · Cited by 280 · cited 1× · see citing works
“Immunohistochemical analyses using the MyHC-IIb-specific antibody BF-F3 [23] appeared to indicate an increased immunoreactivity in DMD samples as compared to control samples but the data were inconsistent.”
ResultCharacterization of human skeletal muscle fibres according to the myosin heavy chains they express
Ennion, S. J., Pereira, J. S. A., Sargeant, A. J., Young, A., & Goldspink, G. (1995) · Journal of Muscle Research and Cell Motility · doi:10.1007/bf00125308 · Cited by 239 · cited 2× · see citing works
“This speciesto-species variation in MyHC isoform expression is, perhaps, most notable for MyHC-IIb, which is the predominant MyHC isoform expressed in most small rodent muscles yet effectively not expressed in the vast majority of adult human skeletal muscle [6,7,10].”
BackgroundExpression of myosin isoforms during notexin-induced regeneration of rat soleus muscles
Whalen, R. G., Harris, J. B., Butler-Browne, G. S., & Sesodia, S. (1990) · Developmental Biology · doi:10.1016/0012-1606(90)90099-5 · Cited by 235 · cited 1× · see citing works
“Given that muscle fibre regeneration is characterized by a recapitulation of developmental programmes of gene expression that includes re-expression of the developmental myosin heavy chain isoforms and myogenic regulatory factors [19-22], we also wished to see if there was any evidence of MyHC-IIb expression in post-n…”
BackgroundWeiss, A., Schiaffino, S., & Leinwand, L. A. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.2865 · Cited by 227 · cited 2× · see citing works
“Given that the human MyHC-IIb gene is intact, highly conserved with the mouse MyHCIIb gene and capable of producing functional, enzymatically active myosin if expressed as recombinant protein [1,2,9,14], we sought to elucidate the molecular * Correspondence: leslie.”
BackgroundSelf-citationOrganization of human and mouse skeletal myosin heavy chain gene clusters is highly conserved
Weiss, A., McDonough, D., Wertman, B., Acakpo‐Satchivi, L., Montgomery, K. T., Kucherlapati, R., Leinwand, L. A., & Krauter, K. S. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.6.2958 · Cited by 191 · cited 3× · see citing works
“Given that the human MyHC-IIb gene is intact, highly conserved with the mouse MyHCIIb gene and capable of producing functional, enzymatically active myosin if expressed as recombinant protein [1,2,9,14], we sought to elucidate the molecular * Correspondence: leslie.”
BackgroundSelf-citationMuscle, Genes and Athletic Performance
Andersen, J. L., Schjerling, P., & Saltin, B. (2000) · Scientific American · doi:10.1038/scientificamerican0900-48 · Cited by 155 · cited 1× · see citing works
“Despite this potential incompatibility, it has also been suggested that the MyHC-IIb gene might be a target for ‘gene doping’ manipulations designed to improve human athletic performance [12,13].”
BackgroundDifferent Pathways Regulate Expression of the Skeletal Myosin Heavy Chain Genes
Allen, D. L., Sartorius, C. A., Sycuro, L. K., & Leinwand, L. A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m108017200 · Cited by 152 · cited 1× · see citing works
“0 kb of the proximal mouse MyHC-IIb promoter region is sufficient to confer both muscle and fibre-type specificity [1,15-18], we began our investigation by aligning ~1.”
BackgroundSelf-citationFunctional diversity among a family of human skeletal muscle myosin motors
Resnicow, D. I., Deacon, J. C., Warrick, H. M., Spudich, J. A., & Leinwand, L. A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0913527107 · Cited by 116 · cited 1× · see citing works
“Given that the human MyHC-IIb gene is intact, highly conserved with the mouse MyHCIIb gene and capable of producing functional, enzymatically active myosin if expressed as recombinant protein [1,2,9,14], we sought to elucidate the molecular * Correspondence: leslie.”
BackgroundSelf-citationRegulation of skeletal muscle fiber size, shape and function
Edgerton, V. R., & Roy, R. R. (1991) · Journal of Biomechanics · doi:10.1016/0021-9290(91)90383-x · Cited by 104 · cited 1× · see citing works
“The expression of a particular MyHC isoform within an individual muscle fibre confers specific morphological, enzymatic and functional effects on that muscle fibre such that MyHC-b-expressing fibres are typically smaller, slower contracting fibres rich in the enzymes of oxidative metabolism while MyHC-IIb-expressing f…”
BackgroundFetal myosin immunoreactivity in human dystrophic muscle
Schiaffino, S., Gorza, L., Dones, I., Cornelio, F., & Sartore, S. (1986) · Muscle & Nerve · doi:10.1002/mus.880090108 · Cited by 94 · cited 1× · see citing works
“Given that muscle fibre regeneration is characterized by a recapitulation of developmental programmes of gene expression that includes re-expression of the developmental myosin heavy chain isoforms and myogenic regulatory factors [19-22], we also wished to see if there was any evidence of MyHC-IIb expression in post-n…”
BackgroundMuscle fiber types and function
Talmadge, R. J., Roy, R. R., & Edgerton, V. R. (1993) · Current Opinion in Rheumatology · doi:10.1097/00002281-199305060-00002 · Cited by 80 · see citing works
Sant'Ana, J. A. A. P., Ennion, S. J., Sargeant, A. J., Moorman, A. F. M., & Goldspink, G. (1997) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s004240050495 · Cited by 76 · cited 3× · see citing works
“As mentioned above, MyHC-IIb expression is typically associated with high forces of contraction combined with rapid contractile characteristics and it has been suggested that the contractile characteristics of MyHCIIb may be incompatible with the biomechanical constraints of larger muscles [7,11].”
BackgroundAllen, D. L., Harrison, B. C., Sartorius, C. A., Byrnes, W. C., & Leinwand, L. A. (2001) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.2001.280.3.c637 · Cited by 76 · cited 2× · see citing works
“This speciesto-species variation in MyHC isoform expression is, perhaps, most notable for MyHC-IIb, which is the predominant MyHC isoform expressed in most small rodent muscles yet effectively not expressed in the vast majority of adult human skeletal muscle [6,7,10].”
BackgroundSelf-citationAbundant expression of myosin heavy-chain IIB RNA in a subset of human masseter muscle fibres
HORTON, M. J., Brandon, C. A., Morris, T. J., Braun, T. W., Yaw, K. M., & Sciote, J. J. (2001) · Archives of Oral Biology · doi:10.1016/s0003-9969(01)00066-8 · Cited by 70 · cited 3× · see citing works
“Given that the human MyHC-IIb gene is intact, highly conserved with the mouse MyHCIIb gene and capable of producing functional, enzymatically active myosin if expressed as recombinant protein [1,2,9,14], we sought to elucidate the molecular * Correspondence: leslie.”
BackgroundIn vivo analysis of the myosin heavy chain IIB promoter region
Swoap, S. J. (1998) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1998.274.3.c681 · Cited by 67 · cited 1× · see citing works
“0 kb of the proximal mouse MyHC-IIb promoter region is sufficient to confer both muscle and fibre-type specificity [1,15-18], we began our investigation by aligning ~1.”
BackgroundNew Perspectives About Human Laryngeal Muscle
Wu, Y. Z., Crumley, R. L., Armstrong, W. B., & Caiozzo, V. J. (2000) · Archives of Otolaryngology - Head and Neck Surgery · doi:10.1001/archotol.126.7.857 · Cited by 66 · see citing works
Alley, R. B. (2004) · Scientific American · doi:10.1038/scientificamerican1104-62 · Cited by 58 · see citing works
Lakich, M. M., Diagana, T. T., North, D. L., & Whalen, R. G. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.24.15217 · Cited by 55 · cited 16× · see citing works
“The mouse AT2 region showed strong binding of a protein that was supershifted by a myocyte enhancer factor 2 (MEF2)-specific antibody.”
BackgroundInfluentialTakeda, S., North, D. L., Diagana, T. T., Miyagoe, Y., Lakich, M. M., & Whalen, R. G. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.26.15664 · Cited by 41 · cited 14× · see citing works
“The mouse AT2 region showed strong binding of a protein that was supershifted by a myocyte enhancer factor 2 (MEF2)-specific antibody.”
BackgroundInfluentialSweeney, H. L. (2004) · Scientific American · doi:10.1038/scientificamerican0704-62 · Cited by 35 · see citing works
Expression of myogenic regulatory factors (MRFs) in human neuromuscular disorders
Olivé, M., Martínez‐Matos, J. A., Pirretas, P., Povedano, M., Navarro, C., & Ferrer, I. (1997) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.1997.tb01324.x · Cited by 30 · cited 23× · see citing works
“The mouse AT2 region showed strong binding of a protein that was supershifted by a myocyte enhancer factor 2 (MEF2)-specific antibody.”
BackgroundInfluentialParham, D. M., Bertoríni, T. E., Dias, P., von Wronski, M. A., Houghton, P. J., Bertorim, T., & HORNER, L. H. (1994) · Acta Neuropathologica · doi:10.1007/bf00293322 · Cited by 12 · cited 14× · see citing works
“The mouse AT2 region showed strong binding of a protein that was supershifted by a myocyte enhancer factor 2 (MEF2)-specific antibody.”
BackgroundInfluential
Flagged first, then by citations
Cited by
Sorted by citations
Sex-Based Differences in Skeletal Muscle Kinetics and Fiber-Type Composition
Haizlip, K. M., Harrison, B. C., & Leinwand, L. A. (2015) · Physiology · doi:10.1152/physiol.00024.2014 · Cited by 521 · see citing works
“In contrast, human skeletal muscle does not express MyHC-IIb protein, a phenomenon that appears to be, at least in part, due to a reduction in the activity of the human MyHC-IIb promoter region (37).”
BackgroundSelf-citationSingle Muscle Fiber Proteomics Reveals Fiber-Type-Specific Features of Human Muscle Aging
Murgia, M., Toniolo, L., Nagaraj, N., Ciciliot, S., Vindigni, V., Schiaffino, S., Reggiani, C., & Mann, M. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.05.054 · Cited by 315 · see citing works
“The expression of MYH4, specific for the fastest 2B fiber type, was negligible as expected (Harrison et al., 2011).”
BackgroundOverview of the Muscle Cytoskeleton
Henderson, C. A., Gomez, C. G., Novak, S. M., Mi‐Mi, L., & Gregorio, C. C. (2017) · Comprehensive physiology · doi:10.1002/cphy.c160033 · Cited by 305 · see citing works
“present only in a very small subset of specialized muscle, but is observed to re-activate in limb muscle undergoing regeneration after profound degeneration (242).”
The mdx mouse model as a surrogate for D uchenne muscular dystrophy
Partridge, T. A. (2013) · FEBS Journal · doi:10.1111/febs.12267 · Cited by 187 · see citing works
Deshmukh, A. S., Steenberg, D. E., Hostrup, M., Birk, J. B., Larsen, J. K., Santos, A., Kjøbsted, R., Hingst, J. R., Schéele, C., Murgia, M., et al. (2021) · Nature Communications · doi:10.1038/s41467-020-20556-8 · Cited by 169 · see citing works
Starring or supporting role? Satellite cells and skeletal muscle fiber size regulation
Murach, K. A., Fry, C. S., Kirby, T. J., Jackson, J. R., Lee, J. D., White, S. H., Dupont-Versteegden, E. E., McCarthy, J. J., & Peterson, C. A. (2018) · Physiology · doi:10.1152/physiol.00019.2017 · Cited by 137 · see citing works
“A caveat to the interpretation of plantaris overload studies is that the mouse plantaris is composed primarily of fast-twitch MyHC type 2a, 2x, and 2b muscle fibers; humans do not generally express the MyHC type 2b protein but do express MyHC type 2x (69, 172).”
BackgroundGuess, M. G., Bjorkman, K. K., Harrison, B. C., & Leinwand, L. A. (2015) · PLoS ONE · doi:10.1371/journal.pone.0118229 · Cited by 94 · see citing works
“Eric Hoffman (George Washington University) and have been described previously [47].”
MethodSelf-citationMyosin heavy chain mRNA isoforms are expressed in two distinct cohorts during C2C12 myogenesis
Brown, D. M., Parr, T., & Brameld, J. M. (2011) · Journal of Muscle Research and Cell Motility · doi:10.1007/s10974-011-9267-4 · Cited by 98 · see citing works
“…muscle is composed of four major muscle fibre types (type I, IIa, IIx and IIb; Lefaucheur 2010) with two further isoforms, embryonic (emb) and neonatal (neo), which are generally only expressed during development or states of muscle regeneration (Harrison et al. 2011; D'Antona et al. 2006).”
BackgroundInfluentialClinical Classification of Cancer Cachexia: Phenotypic Correlates in Human Skeletal Muscle
Johns, N., Hatakeyama, S., Stephens, N. A., Degen, M., Degen, S., Frieauff, W., Lambert, C., Ross, J. A., Roubenoff, R., Glass, D. J., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0083618 · Cited by 94 · see citing works
“Immunohistology for type I and IIa resulted in complementary staining in general, whereas fibre type IIb resulted in very low staining intensity as reported elsewhere [19]; therefore quantitative analysis was done only with type I and IIa but not with type IIb (Table 2).”
ResultmicroRNAs: Modulators of the underlying pathophysiology of sarcopenia?
Brown, D. M., & Goljanek‐Whysall, K. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.08.007 · Cited by 75 · see citing works
Santos, M. D., Backer, S., Aurade, F., Wong, M. M.-K., Wurmser, M., Pierre, R., Vives, F. L., Cruzeiro, M. D., Schmitt, A., Concordet, J., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28666-1 · Cited by 72 · see citing works
Recessive MYL2 mutations cause infantile type I muscle fibre disease and cardiomyopathy
Weterman, M. A. J., Barth, P. G., van Spaendonck‐Zwarts, K. Y., Aronica, E., Poll‐The, B. T., Brouwer, O. F., van Tintelen, J. P., Qahar, Z., Bradley, E. J., de Wissel, M. B., et al. (2013) · Brain · doi:10.1093/brain/aws293 · Cited by 56 · see citing works
The ancient sarcomeric myosins found in specialized muscles
Lee, L. A., Karabina, A., Broadwell, L. J., & Leinwand, L. A. (2019) · Skeletal Muscle · doi:10.1186/s13395-019-0192-3 · Cited by 56 · see citing works
Self-citationKelly, S. A., Bell, T. A., Selitsky, S. R., Buus, R. J., Hua, K., Weinstock, G. M., Garland, T., de Villena, F. P., & Pomp, D. (2013) · Genetics · doi:10.1534/genetics.113.154476 · Cited by 45 · see citing works
Overview of the Muscle Cytoskeleton
Henderson, C. A., Gomez, C. G., Novak, S. M., Mi‐Mi, L., & Gregorio, C. C. (2017) · Comprehensive physiology · doi:10.1002/j.2040-4603.2017.tb00766.x · Cited by 43 · see citing works
The Effect of Serum Origin on Tissue Engineered Skeletal Muscle Function
Khodabukus, A., & Baar, K. (2014) · Journal of Cellular Biochemistry · doi:10.1002/jcb.24938 · Cited by 40 · see citing works
“Humans show a similar diversity offiber types, but lack the IIb MHC gene [Harrison et al., 2011].”
BackgroundFibre typing of intrafusal fibres
Thornell, L., Carlsson, L. M. S., Eriksson, P., Liu, J., Österlund, C., Stål, P., & Domellöf, F. P. (2015) · Journal of Anatomy · doi:10.1111/joa.12338 · Cited by 39 · see citing works
“Expression of MyHC-IIb mRNA has been observed in foetal human myotubes and in Duchenne Muscular Dystrophy skeletal muscle, but there was no compelling evidence for expression of the MyHC-IIb protein (Harrison et al. 2011).”
BackgroundBloemink, M. J., Deacon, J. C., Resnicow, D. I., Leinwand, L. A., & Geeves, M. A. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.488130 · Cited by 38 · see citing works
“isoform MyHC-IIb, which is the predominant myosin in the fast skeletal fibers of rodents, is not expressed in healthy human muscles; however, the gene is present and encodes a functional motor (11), and its RNA is detectable in the muscles of patients with Duchenne muscular dystrophy (12).”
BackgroundSelf-citationPeggion, C., Massimino, M. L., Biancotto, G., Angeletti, R., Reggiani, C., Sorgato, M. C., Bertoli, A., & Stella, R. (2017) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-016-0160-2 · Cited by 38 · see citing works
“able in humans and in several other mammalian species, despite the presence of the corresponding gene [12].”
BackgroundInflammatory response during slow- and fast-twitch muscle regeneration
Zimowska, M., Kasprzycka, P., Bocian, K., Delaney, K., Jung, P., Kuchcinska, K., Kaczmarska, K., Gladysz, D., Stremińska, W., & Ciemerych, M. A. (2016) · Muscle & Nerve · doi:10.1002/mus.25246 · Cited by 37 · see citing works
“The dynamics of its expression may differ, however, depending on the method of muscle injury.(11,12,29,36,37,48) Nevertheless, it marks newly formed muscle fibers.”
BackgroundMethodCasini, N., Forte, I. M., Mastrogiovanni, G., Pentimalli, F., Angelucci, A., Festuccia, C., Tomei, V., Ceccherini, E., Marzo, D. D., Schenone, S., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.3043 · Cited by 26 · see citing works
Oct-1 recruitment to the nuclear envelope in adult-onset autosomal dominant leukodystrophy
Columbaro, M., Mattioli, E., Maraldi, N. M., Ortolani, M., Gasparini, L., D’Apice, M. R., Postorivo, D., Nardone, A. M., Avnet, S., Cortelli, P., et al. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2012.12.006 · Cited by 26 · see citing works
“Based on published data [23,32,33] and on our results here reported, we propose a model”
Krag, T. O. B., & Vissing, J. (2015) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000260 · Cited by 23 · see citing works
“This may be caused by the ongoing degeneration/regeneration cycle, which favors MHC IIB expression, as seen in mice undergoing atrophy while in space flight and in patients with Duchenne muscular dystrophy (33, 34).”
BackgroundAnalysis of human satellite cell dynamics on cultured adult skeletal muscle myofibers
Feige, P., Tsai, E. C., & Rudnicki, M. A. (2021) · Skeletal Muscle · doi:10.1186/s13395-020-00256-z · Cited by 22 · see citing works
Differential regulation of myofibrillar proteins in skeletal muscles of septic mice
Moarbes, V., Mayaki, D., Huck, L., Leblanc, P., Vassilakopoulos, T., Petrof, B. J., & Hussain, S. N. A. (2019) · Physiological Reports · doi:10.14814/phy2.14248 · Cited by 22 · see citing works
“Myocyte enhancer factor 2 (MEF2), serum response factor (SRF), and Kruppel-like factor 15 (KLF15) are also transcription factors that differentially regulate MHC expression (Harrison et al., 2011; Wang et al., 2014).”
BackgroundSexual dimorphisms in skeletal muscle: current concepts and research horizons
Emmert, M. E., Emmert, A. S., Goh, Q., & Cornwall, R. (2024) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00529.2023 · Cited by 22 · see citing works
Kim, J.-H., Torgerud, W. S., Mosser, K. H. H., Hirai, H., Watanabe, S., Asakura, A., & Thompson, L. V. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2011.00774.x · Cited by 20 · see citing works
“In contrast to healthy muscle, expression of MHCIIB in human skeletal muscles appears to increase with muscle fiber degeneration ⁄ regeneration (Harrison et al., 2011).”
BackgroundPlas, R. L. C., Degens, H., Meijer, J. P. (., de Wit, G. M. J., Philippens, I. H. C. H. M., Bobbert, M. F., & Jaspers, R. T. (2015) · Journal of Experimental Biology · doi:10.1242/jeb.117655 · Cited by 18 · see citing works
“The lack of IIB MHC expression in human skeletal muscle is due to specific, key promoter sequences of the human gene which differ from those of the mouse IIB MHC gene (Harrison et al., 2011).”
BackgroundInfluentialAsaduzzaman, M., Kinoshita, S., Siddique, B. S., Asakawa, S., & Watabe, S. (2011) · Gene · doi:10.1016/j.gene.2011.08.005 · Cited by 18 · see citing works
Determination of Muscle Fiber Type in Rodents
Kalmár, B., Blanco, G., & Greensmith, L. (2012) · Current Protocols in Mouse Biology · doi:10.1002/9780470942390.mo110229 · Cited by 16 · see citing works
“The reason for this change of myosin isoform ex- pression has been attributed to nucleotide differences that eliminate binding sites for myocyte enhancer factor 2 (MEF2) and serum response factor (SRF) in the promotor of the human MYH4 gene (Brooke et al., 2011).”
BackgroundPost-transcriptional modulation of interleukin 8 by CNOT6L regulates skeletal muscle differentiation
Polesskaya, A., Pinna, G., Sassi, Y., Vandamme, M., Bigot, A., Mouly, V., Morozova, N., Harel‐Bellan, A., & Degerny, C. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2015.11.018 · Cited by 15 · see citing works
“As Glut4 [6] and different fiber-type specific MHC isoforms [7] are also commonly used as myocyte differentiation markers, we analyzed their expression levels in proliferating and differentiating LHCN cells by RT-qPCR.”
MethodBaltušnikas, J., Venckūnas, T., Kilikevičius, A., Fokin, A., & Ratkevičius, A. (2015) · PubMed Central · Cited by 15 · see citing works
Ahammad, A. K. S., Asaduzzaman, M., Ceyhun, S. B., Ceylan, H., Asakawa, S., Watabe, S., & Kinoshita, S. (2018) · Gene · doi:10.1016/j.gene.2018.11.040 · Cited by 15 · see citing works
Myosin Heavy Chain-2b Transcripts and Isoform Are Expressed in Human Laryngeal Muscles
Smerdu, V., & Cvetko, E. (2013) · Cells Tissues Organs · doi:10.1159/000351293 · Cited by 15 · see citing works
Sosnicki, A. A., Gonzalez, J. M., Fields, B., & Knap, P. W. (2024) · Meat Science · doi:10.1016/j.meatsci.2024.109676 · Cited by 12 · see citing works
A mechanistic basis of fast myofiber vulnerability to neuromuscular diseases
Santos, M. D., Bezprozvannaya, S., McAnally, J., Cai, C., Liu, N., & Olson, E. N. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115959 · Cited by 12 · see citing works
“33 However, the human Myh4 promoter retains a conserved Maf recognition element, suggesting that Maf may activate Myh4 gene in humans.”
Sadaki, S., Tsuji, R., Hayashi, T., Watanabe, M., Iwai, R., Wenchao, G., Semenova, E. A., Илгизович, С. Р., Викторович, Ж. А., Generozov, E. V., et al. (2025) · Skeletal Muscle · doi:10.1186/s13395-025-00391-5 · Cited by 12 · see citing works
“MYH4 mRNA was previously detected in a small sub-set of specialized muscles, such as the human masseter and laryngeal muscles, as well as in skeletal muscle from patients with Duchenne muscular dystrophy [25, 50, 66].”
Pandorf, C., Haddad, F., Owerkowicz, T., Carroll, L. P., Baldwin, K., & Adams, G. (2020) · American Journal of Physiology - Cell Physiology · doi:10.1152/ajpcell.00166.2018 · Cited by 7 · see citing works
Brown, D. M., Brameld, J. M., & Parr, T. (2014) · PLoS ONE · doi:10.1371/journal.pone.0114365 · Cited by 10 · see citing works
“Furthermore, we also show that although both the pig and human MYH4 promoters are responsive to a known MYH4 inducing stimulus, such as MyoD over-expression [10, 30, 32], the absolute capacity to activate the human MYH4 promoter was limited in comparison to the equivalent pig promoter, suggesting that sequence differe…”
BackgroundMethodInfluentialA perspective on muscle phenotyping in musculoskeletal research
Foessl, I., Ackert‐Bicknell, C. L., Kague, É., Laskou, F., Jakob, F. J., Karasik, D., Obermayer-Pietsch, B. M., Alonso, N., Bjørnerem, Å., Brandi, M. L., et al. (2024) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2024.01.004 · Cited by 8 · see citing works
Hitachi, K., Kiyofuji, Y., Yamaguchi, H., Nakatani, M., Inui, M., & Tsuchida, K. (2022) · The FASEB Journal · doi:10.1096/fj.202200581r · Cited by 7 · see citing works
Sanz‐Nogués, C., Keane, A. J., Creane, M., Hynes, S. O., Chen, X., Lyons, C. J., Horan, E., Elliman, S. J., Goljanek‐Whysall, K., & O’Brien, T. (2024) · Stem Cells · doi:10.1093/stmcls/sxae058 · Cited by 6 · see citing works
Gomi, T., Okuda, I., Seino, A., Ohara, K., & Harada, Y. (2025) · Scientific Reports · doi:10.1038/s41598-025-89138-2 · Cited by 6 · see citing works
Lrrc75b is a novel negative regulator of C2C12 myogenic differentiation
Zhong, Y.-C., Zou, L., Wang, Z., Pan, Y., Dai, Z., Liu, X., Cui, L., & Zuo, C. (2016) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2016.2738 · Cited by 5 · see citing works
Shah, F. K., Stål, P., Li, J., Sessle, B. J., & Avivi‐Arber, L. (2019) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2019.01.009 · Cited by 5 · see citing works
Brearley-Sholto, M. C., Loczenski-Brown, D. M., Loughna, P. T., Parr, T., & Brameld, J. M. (2021) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2021.100924 · Cited by 5 · see citing works
“Increased expression of MyHC-IIB is often associated with muscle hypertrophy, therefore this characteristic has most likely developed as a result of intensive breeding for enhanced muscle growth traits [8,9].”
BackgroundHuman and African ape myosin heavy chain content and the evolution of hominin skeletal muscle
Queeno, S. R., Reiser, P. J., Orr, C. M., Capellini, T. D., Sterner, K. N., & O’Neill, M. C. (2023) · Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology · doi:10.1016/j.cbpa.2023.111415 · Cited by 5 · see citing works
Burke, M. J., Blatt, B. M., Teixeira, J. A., Pérez‐López, D. O., Yue, Y., Pan, X., Hakim, C. H., Yao, G., Herzog, R. W., & Duan, D. (2025) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.13681 · Cited by 4 · see citing works
“Consistent with the literature, these muscles did not contain Type IIb myofibres, a characteristic feature of human and dog, but not mouse muscles [13].”
InfluentialFazio, E., Lindner, A., Cravana, C., Wegener, J., Medica, P., Hartmann, U., & Ferlazzo, A. (2021) · Journal of Equine Veterinary Science · doi:10.1016/j.jevs.2021.103853 · Cited by 4 · see citing works
Influence of untranslated regions on retroviral mRNA transfer and expression
Prel, A., Sensebé, L., & Pagès, J. (2013) · BMC Biotechnology · doi:10.1186/1472-6750-13-35 · Cited by 4 · see citing works
“We selected 5′ and 3′ UTRs from genes known to have a high level of expression such as vimentin and nonmuscular myosin heavy chain (NMHC) [21,22].”
BackgroundExpression of MyHC‐15 and ‐ 2x in human muscle spindles: An immunohistochemical study
Smerdu, V. (2023) · Journal of Anatomy · doi:10.1111/joa.13923 · Cited by 3 · see citing works
“MyHC-2b mRNA transcripts were previously detected in the masseter muscle and in patients with Duchenne muscular dystrophy (Harrison et al., 2011 ; Horton et al., 2001 ), but not the corresponding protein, in the latter study using antibody BF-F3.”
Muscle Fibre Phenotyping from a Single Section: Is It as Informative as from Serial Sections?
Meznarič, M., & Erze, I. (2012) · InTech eBooks · doi:10.5772/47845 · Cited by 3 · see citing works
“The forth skeletal muscle-specific isoform MyHC-IIB, is expressed in mice and rat skeletal muscles and is thought not to be expressed in adult human muscles at the protein level; however MyHC-IIB mRNA has been detected in specialized human muscles (8, 9) and in limb muscles of patients suffering from Duchenne muscular…”
BackgroundBarrett, P., Quick, T., Mudera, V., & Player, D. J. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.760260 · Cited by 3 · see citing works
“, 2003) expressed in adult mice, associated with high forces of contraction combined with rapid contractile characteristics (Harrison et al., 2011).”
BackgroundHenning, F., & Kohn, T. A. (2022) · Journal of Muscle Research and Cell Motility · doi:10.1007/s10974-022-09638-w · Cited by 3 · see citing works
Yang, Y., Tan, B., Xiao, L., Huang, H., Xu, W., Su, J., Zhao, Y., Hong, L., Cai, G., Li, Z., et al. (2025) · Gene · doi:10.1016/j.gene.2025.149578 · Cited by 2 · see citing works
Profiling the epigenomic landscape of late embryonic and adult mouse hind limb muscles
Queeno, S. R., Okamoto, A. S., Callahan, D. M., O’Neill, M. C., Capellini, T. D., & Sterner, K. N. (2026) · Scientific Reports · doi:10.1038/s41598-025-32705-4 · Cited by 1 · see citing works
Sayed, R. K. A., Lange, A. N., Paez, H. G., Hibbert, J. E., Meinhold, M., Flynn, C. G. K., Vergara, M. B. Z., Dobrzycki, I., Wrucke, D. J., Zepeda, C. S., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.16.706166 · Cited by 1 · see citing works
(2020) · Elsevier eBooks · doi:10.1016/b978-0-7020-7471-4.00003-3
A tissue engineered human skeletal muscle model for use in exercise sciences
Martin, N. R. W. (2012) · University of Bedfordshire Repository (University of Bedfordshire)
Feige, P., Tsai, E. C., & Rudnicki, M. A. (2021) · Figshare · doi:10.6084/m9.figshare.13521025
Sayed, R. K. A., Lange, A. N., Paez, H. G., Hibbert, J. E., Meinhold, M., Flynn, C. G. K., Hartung, J., Santibanez, M. B. Z., Dobrzycki, I., Wrucke, D. J., et al. (2026) · The Journal of Physiology · doi:10.1113/jp291728
“A3) (Harrison et al., 2011; Zhu et al., 2021).”
- Authors
- Harrison, B. C., Allen, D. L., & Leinwand, L. A.
- Affiliations
- University of Colorado Boulder (US)
- Corresponding author
- Leinwand, Leslie A
- Venue
- Skeletal Muscle
- Published
- 2011-02-01
- Volume
- 1
- Issue
- 1
- Pages
- 5-5
- ISSN
- 2044-5040 (ISSN-L)
- PMC
- PMC3143903
- OpenAlex
- W2150832401
- Cited by
- 64
- References
- 23
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 4 · 2023: 4 · 2022: 4 · 2021: 6 · 2020: 2 · 2019: 3 · 2018: 1 · 2017: 5 · 2016: 2 · 2015: 9 · 2014: 3 · 2013: 6 · 2012: 4
- FWCI
- 2.08
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Skeletal Muscle (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (K01AR055676)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- gene expression regulation, serum response factor, human-mouse sequence comparison, fetal muscle, Duchenne muscular dystrophy, muscle degeneration and regeneration, limb muscles, transcriptional regulation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
