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Epigenetics and muscle dysfunction in chronic obstructive pulmonary disease

  • Esther Barreiro
    Correspondence
    Reprint requests: Esther Barreiro, Pulmonology Department and Lung Cancer Research Group, IMIM-Hospital del Mar, PRBB, Dr Aiguader, 88, E-08003 Barcelona, Spain
    Affiliations
    Respiratory Medicine Department-Muscle and Respiratory System Research Unit, Institute of Medical Research of Hospital del Mar (IMIM)-Hospital del Mar, Parc de Salut Mar, Barcelona Biomedical Research Park (PRBB), Barcelona, Spain

    Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
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  • Joaquim Gea
    Affiliations
    Respiratory Medicine Department-Muscle and Respiratory System Research Unit, Institute of Medical Research of Hospital del Mar (IMIM)-Hospital del Mar, Parc de Salut Mar, Barcelona Biomedical Research Park (PRBB), Barcelona, Spain

    Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
    Search for articles by this author
Published:April 17, 2014DOI:https://doi.org/10.1016/j.trsl.2014.04.006
      Chronic obstructive pulmonary disease (COPD) is a common, preventable, and treatable disease and a major leading cause of morbidity and mortality worldwide. In COPD, comorbidities, acute exacerbations, and systemic manifestations negatively influence disease severity and progression regardless of the respiratory condition. Skeletal muscle dysfunction, which is one of the commonest systemic manifestations in patients with COPD, has a tremendous impact on their exercise capacity and quality of life. Several pathophysiological and molecular underlying mechanisms including epigenetics (the process whereby gene expression is regulated by heritable mechanisms that do not affect DNA sequence) have been shown to participate in the etiology of COPD muscle dysfunction. The epigenetic modifications identified so far in cells include DNA methylation, histone acetylation and methylation, and noncoding RNAs such as microRNAs. Herein, we first review the role of epigenetic mechanisms in muscle development and adaptation to environmental factors in several models. Moreover, the epigenetic events reported so far to be potentially involved in muscle dysfunction and mass loss of patients with COPD are also discussed. Furthermore, the different expression profile of several muscle-enriched microRNAs in the diaphragm and vastus lateralis muscles of patients with COPD are also reviewed from results recently obtained in our group. The role of protein hyperacetylation in enhanced muscle protein catabolism of limb muscles is also discussed. Future research should focus on the full elucidation of the triggers of epigenetic mechanisms and their specific downstream biological pathways in COPD muscle dysfunction and wasting.

      Abbreviations:

      ANOVA (Analysis of variance), COPD (chronic obstructive pulmonary disease), MyHC (myosin heavy chain), CH3 (methyl group), coA (coenzyme A), CpG (cytosine and guanosine nucleotides), DNA (deoxyribonucleic acid), HSP (heat shock proteins), HTAs (histone acetyltransferases), HDACs (histone deacetylases), H3K4me3 (histone H3 trimethyl Lys4), Hox-A11 (homeobox A11), IGF-1 (insulin-like growth factor-1), NAD (nicotinamide adenine dinucleotide), PHD (plant homeodomains), MRTF (myocardin-related transcription factors), MEF2 (myocyte-enhancing factor), Myf-5 (myogenic factor 5), pax7 (paired box protein), PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha), SRF (serum response factor), TGF (transforming growth factor), RNA (ribonucleic acid), RISC (RNA-induced silencing complex), SIRT (sirtuin), YY1 (Yin Yang 1)
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      References

        • Vestbo J.
        • Hurd S.S.
        • Agusti A.G.
        • et al.
        Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.
        Am J Respir Crit Care Med. 2013; 187: 347-365
        • Miravitlles M.
        • Soler-Cataluna J.J.
        • Calle M.
        • et al.
        Spanish COPD Guidelines (GesEPOC): pharmacological treatment of stable COPD. Spanish Society of Pulmonology and Thoracic Surgery.
        Arch Bronconeumol. 2012; 48: 247-257
        • Miravitlles M.
        • Calle M.
        • Soler-Cataluna J.J.
        Clinical phenotypes of COPD: identification, definition and implications for guidelines.
        Arch Bronconeumol. 2012; 48: 86-98
        • Alamdari N.
        • Aversa Z.
        • Castillero E.
        • Hasselgren P.O.
        Acetylation and deacetylation—novel factors in muscle wasting.
        Metabolism. 2013; 62: 1-11
        • Lewis A.
        • Riddoch-Contreras J.
        • Natanek S.A.
        • et al.
        Downregulation of the serum response factor/miR-1 axis in the quadriceps of patients with COPD.
        Thorax. 2012; 67: 26-34
        • Gosselink R.
        • Troosters T.
        • Decramer M.
        Peripheral muscle weakness contributes to exercise limitation in COPD.
        Am J Respir Crit Care Med. 1996; 153: 976-980
        • Seymour J.M.
        • Spruit M.A.
        • Hopkinson N.S.
        • et al.
        The prevalence of quadriceps weakness in COPD and the relationship with disease severity.
        Eur Respir J. 2010; 36: 81-88
        • Marquis K.
        • Debigare R.
        • Lacasse Y.
        • et al.
        Midthigh muscle cross-sectional area is a better predictor of mortality than body mass index in patients with chronic obstructive pulmonary disease.
        Am J Respir Crit Care Med. 2002; 166: 809-813
        • Swallow E.B.
        • Reyes D.
        • Hopkinson N.S.
        • et al.
        Quadriceps strength predicts mortality in patients with moderate to severe chronic obstructive pulmonary disease.
        Thorax. 2007; 62: 115-120
        • Levine S.
        • Bashir M.H.
        • Clanton T.L.
        • Powers S.K.
        • Singhal S.
        COPD elicits remodeling of the diaphragm and vastus lateralis muscles in humans.
        J Appl Physiol. 2013; 114: 1235-1245
        • Gea J.
        • Agusti A.
        • Roca J.
        Pathophysiology of muscle dysfunction in COPD.
        J Appl Physiol. 2013; 114: 1222-1234
        • Mador M.J.
        • Bozkanat E.
        Skeletal muscle dysfunction in chronic obstructive pulmonary disease.
        Respir Res. 2001; 2: 216-224
        • Barreiro E.
        • Schols A.M.
        • Polkey M.
        • et al.
        Cytokine profile in quadriceps muscles of patients with severe COPD.
        Thorax. 2008; 63: 100-107
        • Fermoselle C.
        • Rabinovich R.
        • Ausin P.
        • et al.
        Does oxidative stress modulate limb muscle atrophy in severe COPD patients?.
        Eur Respir J. 2012; 40: 851-862
        • Testelmans D.
        • Crul T.
        • Maes K.
        • et al.
        Atrophy and hypertrophy signalling in the diaphragm of patients with COPD.
        Eur Respir J. 2010; 35: 549-556
        • Marin-Corral J.
        • Minguella J.
        • Ramirez-Sarmiento A.L.
        • Hussain S.N.
        • Gea J.
        • Barreiro E.
        Oxidised proteins and superoxide anion production in the diaphragm of severe COPD patients.
        Eur Respir J. 2009; 33: 1309-1319
        • Ottenheijm C.A.
        • Heunks L.M.
        • Li Y.P.
        • et al.
        Activation of the ubiquitin-proteasome pathway in the diaphragm in chronic obstructive pulmonary disease.
        Am J Respir Crit Care Med. 2006; 174: 997-1002
        • Ottenheijm C.A.
        • Lawlor M.W.
        • Stienen G.J.
        • Granzier H.
        • Beggs A.H.
        Changes in cross-bridge cycling underlie muscle weakness in patients with tropomyosin 3-based myopathy.
        Hum Mol Genet. 2011; 20: 2015-2025
        • Barreiro E.
        • de la Puente B.
        • Minguella J.
        • et al.
        Oxidative stress and respiratory muscle dysfunction in severe chronic obstructive pulmonary disease.
        Am J Respir Crit Care Med. 2005; 171: 1116-1124
        • Barreiro E.
        • Galdiz J.B.
        • Marinan M.
        • Alvarez F.J.
        • Hussain S.N.
        • Gea J.
        Respiratory loading intensity and diaphragm oxidative stress: N-acetyl-cysteine effects.
        J Appl Physiol. 2006; 100: 555-563
        • Barreiro E.
        • Rabinovich R.
        • Marin-Corral J.
        • Barbera J.A.
        • Gea J.
        • Roca J.
        Chronic endurance exercise induces quadriceps nitrosative stress in patients with severe COPD.
        Thorax. 2009; 64: 13-19
        • Barreiro E.
        • Peinado V.I.
        • Galdiz J.B.
        • et al.
        Cigarette smoke-induced oxidative stress: a role in chronic obstructive pulmonary disease skeletal muscle dysfunction.
        Am J Respir Crit Care Med. 2010; 182: 477-488
        • Barreiro E.
        • Ferrer D.
        • Sanchez F.
        • et al.
        Inflammatory cells and apoptosis in respiratory and limb muscles of patients with COPD.
        J Appl Physiol. 2011; 111: 808-817
        • Barreiro E.
        • Sznajder J.I.
        Epigenetic regulation of muscle phenotype and adaptation: a potential role in COPD muscle dysfunction.
        J Appl Physiol. 2013; 114: 1263-1272
        • Casaburi R.
        • Bhasin S.
        • Cosentino L.
        • et al.
        Effects of testosterone and resistance training in men with chronic obstructive pulmonary disease.
        Am J Respir Crit Care Med. 2004; 170: 870-878
        • Coronell C.
        • Orozco-Levi M.
        • Mendez R.
        • Ramirez-Sarmiento A.
        • Galdiz J.B.
        • Gea J.
        Relevance of assessing quadriceps endurance in patients with COPD.
        Eur Respir J. 2004; 24: 129-136
        • Creutzberg E.C.
        • Wouters E.F.
        • Mostert R.
        • Weling-Scheepers C.A.
        • Schols A.M.
        Efficacy of nutritional supplementation therapy in depleted patients with chronic obstructive pulmonary disease.
        Nutrition. 2003; 19: 120-127
        • Creutzberg E.C.
        • Wouters E.F.
        • Mostert R.
        • Pluymers R.J.
        • Schols A.M.
        A role for anabolic steroids in the rehabilitation of patients with COPD? A double-blind, placebo-controlled, randomized trial.
        Chest. 2003; 124: 1733-1742
        • Crul T.
        • Spruit M.A.
        • Gayan-Ramirez G.
        • et al.
        Markers of inflammation and disuse in vastus lateralis of chronic obstructive pulmonary disease patients.
        Eur J Clin Invest. 2007; 37: 897-904
        • Crul T.
        • Testelmans D.
        • Spruit M.A.
        • et al.
        Gene expression profiling in vastus lateralis muscle during an acute exacerbation of COPD.
        Cell Physiol Biochem. 2010; 25: 491-500
        • Decramer M.
        • de Bock V.
        • Dom R.
        Functional and histologic picture of steroid-induced myopathy in chronic obstructive pulmonary disease.
        Am J Respir Crit Care Med. 1996; 153: 1958-1964
        • Donaldson A.
        • Natanek S.A.
        • Lewis A.
        • et al.
        Increased skeletal muscle-specific microRNA in the blood of patients with COPD.
        Thorax. 2013; 68: 1140-1149
        • Doucet M.
        • Russell A.P.
        • Leger B.
        • et al.
        Muscle atrophy and hypertrophy signaling in patients with chronic obstructive pulmonary disease.
        Am J Respir Crit Care Med. 2007; 176: 261-269
        • Fermoselle C.
        • Sanchez F.
        • Barreiro E.
        Reduction of muscle mass mediated by myostatin in an experimental model of pulmonary emphysema.
        Arch Bronconeumol. 2011; 47: 590-598
        • Gayan-Ramirez G.
        • Decramer M.
        Mechanisms of striated muscle dysfunction during acute exacerbations of COPD.
        J Appl Physiol. 2013; 114: 1291-1299
        • Gosker H.R.
        • Zeegers M.P.
        • Wouters E.F.
        • Schols A.M.
        Muscle fibre type shifting in the vastus lateralis of patients with COPD is associated with disease severity: a systematic review and meta-analysis.
        Thorax. 2007; 62: 944-949
        • Laviolette L.
        • Lands L.C.
        • Dauletbaev N.
        • et al.
        Combined effect of dietary supplementation with pressurized whey and exercise training in chronic obstructive pulmonary disease: a randomized, controlled, double-blind pilot study.
        J Med Food. 2010; 13: 589-598
        • Montes de Oca M.
        • Celli B.R.
        Peripheral muscles in COPD: deconditioning or myopathy?.
        Arch Bronconeumol. 2001; 37: 82-87
        • Natanek S.A.
        • Riddoch-Contreras J.
        • Marsh G.S.
        • et al.
        Yin Yang 1 expression and localisation in quadriceps muscle in COPD.
        Arch Bronconeumol. 2011; 47: 296-302
        • Puente-Maestu L.
        • Perez-Parra J.
        • Godoy R.
        • et al.
        Abnormal transition pore kinetics and cytochrome C release in muscle mitochondria of patients with chronic obstructive pulmonary disease.
        Am J Respir Cell Mol Biol. 2009; 40: 746-750
        • Puente-Maestu L.
        • Perez-Parra J.
        • Godoy R.
        • et al.
        Abnormal mitochondrial function in locomotor and respiratory muscles of COPD patients.
        Eur Respir J. 2009; 33: 1045-1052
        • Puente-Maestu L.
        • Lazaro A.
        • Tejedor A.
        • et al.
        Effects of exercise on mitochondrial DNA content in skeletal muscle of patients with COPD.
        Thorax. 2011; 66: 121-127
        • Puente-Maestu L.
        • Tejedor A.
        • Lazaro A.
        • et al.
        Site of mitochondrial reactive oxygen species production in skeletal muscle of chronic obstructive pulmonary disease and its relationship with exercise oxidative stress.
        Am J Respir Cell Mol Biol. 2012; 47: 358-362
        • Puente-Maestu L.
        • Lazaro A.
        • Humanes B.
        Metabolic derangements in COPD muscle dysfunction.
        J Appl Physiol. 2013; 114: 1282-1290
        • Rodriguez D.A.
        • Kalko S.
        • Puig-Vilanova E.
        • et al.
        Muscle and blood redox status after exercise training in severe COPD patients.
        Free Radic Biol Med. 2012; 52: 88-94
        • Swallow E.B.
        • Gosker H.R.
        • Ward K.A.
        • et al.
        A novel technique for nonvolitional assessment of quadriceps muscle endurance in humans.
        J Appl Physiol. 2007; 103: 739-746
        • Vogiatzis I.
        • Terzis G.
        • Nanas S.
        • et al.
        Skeletal muscle adaptations to interval training in patients with advanced COPD.
        Chest. 2005; 128: 3838-3845
        • Vogiatzis I.
        • Stratakos G.
        • Simoes D.C.
        • et al.
        Effects of rehabilitative exercise on peripheral muscle TNFalpha, IL-6, IGF-I and MyoD expression in patients with COPD.
        Thorax. 2007; 62: 950-956
        • Vogiatzis I.
        • Simoes D.C.
        • Stratakos G.
        • et al.
        Effect of pulmonary rehabilitation on muscle remodelling in cachectic patients with COPD.
        Eur Respir J. 2010; 36: 301-310
        • Vogiatzis I.
        • Terzis G.
        • Stratakos G.
        • et al.
        Effect of pulmonary rehabilitation on peripheral muscle fiber remodeling in patients with COPD in GOLD stages II to IV.
        Chest. 2011; 140: 744-752
        • Whittom F.
        • Jobin J.
        • Simard P.M.
        • et al.
        Histochemical and morphological characteristics of the vastus lateralis muscle in patients with chronic obstructive pulmonary disease.
        Med Sci Sports Exerc. 1998; 30: 1467-1474
        • Baar K.
        Epigenetic control of skeletal muscle fibre type.
        Acta Physiol (Oxf). 2010; 199: 477-487
        • Sharma S.
        • Kelly T.K.
        • Jones P.A.
        Epigenetics in cancer.
        Carcinogenesis. 2010; 31: 27-36
        • Lawless M.W.
        • O'Byrne K.J.
        • Gray S.G.
        Targeting oxidative stress in cancer.
        Expert Opin Ther Targets. 2010; 14: 1225-1245
        • Chen L.F.
        • Greene W.C.
        Regulation of distinct biological activities of the NF-kappaB transcription factor complex by acetylation.
        J Mol Med (Berl). 2003; 81: 549-557
        • Sadoul K.
        • Boyault C.
        • Pabion M.
        • Khochbin S.
        Regulation of protein turnover by acetyltransferases and deacetylases.
        Biochimie. 2008; 90: 306-312
        • Seigneurin-Berny D.
        • Verdel A.
        • Curtet S.
        • et al.
        Identification of components of the murine histone deacetylase 6 complex: link between acetylation and ubiquitination signaling pathways.
        Mol Cell Biol. 2001; 21: 8035-8044
        • Scroggins B.T.
        • Robzyk K.
        • Wang D.
        • et al.
        An acetylation site in the middle domain of Hsp90 regulates chaperone function.
        Mol Cell. 2007; 25: 151-159
        • Jacobs S.A.
        • Khorasanizadeh S.
        Structure of HP1 chromodomain bound to a lysine 9-methylated histone H3 tail.
        Science. 2002; 295: 2080-2083
        • Taverna S.D.
        • Ilin S.
        • Rogers R.S.
        • et al.
        Yng1 PHD finger binding to H3 trimethylated at K4 promotes NuA3 HAT activity at K14 of H3 and transcription at a subset of targeted ORFs.
        Mol Cell. 2006; 24: 785-796
        • Cote J.
        • Richard S.
        Tudor domains bind symmetrical dimethylated arginines.
        J Biol Chem. 2005; 280: 28476-28483
        • Huang Y.
        • Fang J.
        • Bedford M.T.
        • Zhang Y.
        • Xu R.M.
        Recognition of histone H3 lysine-4 methylation by the double tudor domain of JMJD2A.
        Science. 2006; 312: 748-751
        • Angulo M.
        • Lecuona E.
        • Sznajder J.I.
        Role of MicroRNAs in lung disease.
        Arch Bronconeumol. 2012; 48: 325-330
        • Lee Y.
        • Kim M.
        • Han J.
        • et al.
        MicroRNA genes are transcribed by RNA polymerase II.
        EMBO J. 2004; 23: 4051-4060
        • Perdiguero E.
        • Sousa-Victor P.
        • Ballestar E.
        • Munoz-Canoves P.
        Epigenetic regulation of myogenesis.
        Epigenetics. 2009; 4: 541-550
        • Kurihara Y.
        • Watanabe Y.
        Arabidopsis micro-RNA biogenesis through Dicer-like 1 protein functions.
        Proc Natl Acad Sci U S A. 2004; 101: 12753-12758
        • Hutvagner G.
        Small RNA asymmetry in RNAi: function in RISC assembly and gene regulation.
        FEBS Lett. 2005; 579: 5850-5857
        • O'Rourke J.R.
        • Georges S.A.
        • Seay H.R.
        • et al.
        Essential role for Dicer during skeletal muscle development.
        Dev Biol. 2007; 311: 359-368
        • Deato M.D.
        • Marr M.T.
        • Sottero T.
        • Inouye C.
        • Hu P.
        • Tjian R.
        MyoD targets TAF3/TRF3 to activate myogenin transcription.
        Mol Cell. 2008; 32: 96-105
        • Nakajima N.
        • Takahashi T.
        • Kitamura R.
        • et al.
        MicroRNA-1 facilitates skeletal myogenic differentiation without affecting osteoblastic and adipogenic differentiation.
        Biochem Biophys Res Commun. 2006; 350: 1006-1012
        • Lucarelli M.
        • Fuso A.
        • Strom R.
        • Scarpa S.
        The dynamics of myogenin site-specific demethylation is strongly correlated with its expression and with muscle differentiation.
        J Biol Chem. 2001; 276: 7500-7506
        • Palacios D.
        • Puri P.L.
        The epigenetic network regulating muscle development and regeneration.
        J Cell Physiol. 2006; 207: 1-11
        • Guenther M.G.
        • Levine S.S.
        • Boyer L.A.
        • Jaenisch R.
        • Young R.A.
        A chromatin landmark and transcription initiation at most promoters in human cells.
        Cell. 2007; 130: 77-88
        • Kuang S.
        • Kuroda K.
        • Le G.F.
        • Rudnicki M.A.
        Asymmetric self-renewal and commitment of satellite stem cells in muscle.
        Cell. 2007; 129: 999-1010
        • McKinnell I.W.
        • Ishibashi J.
        • Le G.F.
        • et al.
        Pax7 activates myogenic genes by recruitment of a histone methyltransferase complex.
        Nat Cell Biol. 2008; 10: 77-84
        • Chen J.F.
        • Mandel E.M.
        • Thomson J.M.
        • et al.
        The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation.
        Nat Genet. 2006; 38: 228-233
        • Elia L.
        • Contu R.
        • Quintavalle M.
        • et al.
        Reciprocal regulation of microRNA-1 and insulin-like growth factor-1 signal transduction cascade in cardiac and skeletal muscle in physiological and pathological conditions.
        Circulation. 2009; 120: 2377-2385
        • Anderson C.
        • Catoe H.
        • Werner R.
        MIR-206 regulates connexin43 expression during skeletal muscle development.
        Nucleic Acids Res. 2006; 34: 5863-5871
        • Dey B.K.
        • Gagan J.
        • Dutta A.
        miR-206 and -486 induce myoblast differentiation by downregulating Pax7.
        Mol Cell Biol. 2011; 31: 203-214
        • Crist C.G.
        • Montarras D.
        • Pallafacchina G.
        • et al.
        Muscle stem cell behavior is modified by microRNA-27 regulation of Pax3 expression.
        Proc Natl Acad Sci U S A. 2009; 106: 13383-13387
        • Naguibneva I.
        • Ameyar-Zazoua M.
        • Polesskaya A.
        • et al.
        The microRNA miR-181 targets the homeobox protein Hox-A11 during mammalian myoblast differentiation.
        Nat Cell Biol. 2006; 8: 278-284
        • Wang H.
        • Garzon R.
        • Sun H.
        • et al.
        NF-kappaB-YY1-miR-29 regulatory circuitry in skeletal myogenesis and rhabdomyosarcoma.
        Cancer Cell. 2008; 14: 369-381
        • Wang L.
        • Zhou L.
        • Jiang P.
        • et al.
        Loss of miR-29 in myoblasts contributes to dystrophic muscle pathogenesis.
        Mol Ther. 2012; 20: 1222-1233
        • Rao P.K.
        • Kumar R.M.
        • Farkhondeh M.
        • Baskerville S.
        • Lodish H.F.
        Myogenic factors that regulate expression of muscle-specific microRNAs.
        Proc Natl Acad Sci U S A. 2006; 103: 8721-8726
        • Zhao Y.
        • Samal E.
        • Srivastava D.
        Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis.
        Nature. 2005; 436: 214-220
        • Allen D.L.
        • Bandstra E.R.
        • Harrison B.C.
        • et al.
        Effects of spaceflight on murine skeletal muscle gene expression.
        J Appl Physiol. 2009; 106: 582-595
        • Aoi W.
        • Naito Y.
        • Mizushima K.
        • et al.
        The microRNA miR-696 regulates PGC-1{alpha} in mouse skeletal muscle in response to physical activity.
        Am J Physiol Endocrinol Metab. 2010; 298: E799-E806
        • McCarthy J.J.
        • Esser K.A.
        MicroRNA-1 and microRNA-133a expression are decreased during skeletal muscle hypertrophy.
        J Appl Physiol. 2007; 102: 306-313
        • Allen D.L.
        • Weber J.N.
        • Sycuro L.K.
        • Leinwand L.A.
        Myocyte enhancer factor-2 and serum response factor binding elements regulate fast myosin heavy chain transcription in vivo.
        J Biol Chem. 2005; 280: 17126-17134
        • Ikeda S.
        • He A.
        • Kong S.W.
        • et al.
        MicroRNA-1 negatively regulates expression of the hypertrophy-associated calmodulin and Mef2a genes.
        Mol Cell Biol. 2009; 29: 2193-2204
        • Wu H.
        • Rothermel B.
        • Kanatous S.
        • et al.
        Activation of MEF2 by muscle activity is mediated through a calcineurin-dependent pathway.
        EMBO J. 2001; 20: 6414-6423
        • Sun Y.
        • Ge Y.
        • Drnevich J.
        • Chen J.
        Mammalian target of rapamycin regulates miRNA-1 and follistatin in skeletal myogenesis.
        J Cell Biol. 2010; 189: 1157-1169
        • Ellis P.D.
        • Martin K.M.
        • Rickman C.
        • Metcalfe J.C.
        • Kemp P.R.
        Increased actin polymerization reduces the inhibition of serum response factor activity by Yin Yang 1.
        Biochem J. 2002; 364: 547-554
        • Wang H.
        • Hertlein E.
        • Bakkar N.
        • et al.
        NF-kappaB regulation of YY1 inhibits skeletal myogenesis through transcriptional silencing of myofibrillar genes.
        Mol Cell Biol. 2007; 27: 4374-4387
        • Alamdari N.
        • Smith I.J.
        • Aversa Z.
        • Hasselgren P.O.
        Sepsis and glucocorticoids upregulate p300 and downregulate HDAC6 expression and activity in skeletal muscle.
        Am J Physiol Regul Integr Comp Physiol. 2010; 299: R509-R520