Down-Regulation of Myogenin Can Reverse Terminal Muscle Cell Differentiation 英文参考文献.docVIP

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Down-Regulation of Myogenin Can Reverse Terminal Muscle Cell Differentiation 英文参考文献.doc

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Down-Regulation of Myogenin Can Reverse Terminal Muscle Cell Differentiation 英文参考文献

Down-RegulationofMyogeninCanReverseTerminal MuscleCellDifferentiation NikolaosP.Mastroyiannopoulos1,PaschalisNicolaou1,MustafaAnayasa1,JamesB.Uney2,LeonidasA. Phylactou1* 1Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus, 2The Henry Wellcome Laboratories for IntegrativeNeuroscienceandEndocrinology,UniversityofBristol,Bristol,UnitedKingdom Abstract Certain higher vertebratesdevelopedthe ability toreverse muscle celldifferentiation (dedifferentiation) asan additional mechanismtoregeneratemuscle.Mammals,ontheotherhand,showlimitedabilitytoreversemusclecelldifferentiation. Myogenic Regulatory Factors (MRFs), MyoD, myogenin, Myf5 and Myf6 are basic-helix-loop-helix (bHLH) transcription factorsessentialtowardstheregulationofmyogenesis. Ourcurrentinterestistoinvestigatewhetherdown-regulationof MRFsinterminallydifferentiatedmousemyotubescaninducereversalofmusclecelldifferentiation.Resultsfromthiswork showed that reduction of myogenin levels in terminally differentiated mouse myotubes can reverse their differentiation state. Down-regulation of myogenin in terminally differentiated mouse myotubes induces cellular cleavage into mononucleated cells and cell cycle re-entry, as shown by re-initiation of DNA synthesis and increased cyclin D1 and cyclin E2 levels. Finally, we provide evidence that down-regulation of myogenin causes cell cycle re-entry (via down- regulationofMyoD)andcellularisationthroughseparatepathways.Thesedatarevealtheimportantroleofmyogeninin maintaining terminal muscle cell differentiation and point to a novel mechanism by which muscle cells could be re- activatedthroughitsdown-regulation. Citation: Mastroyiannopoulos NP, Nicolaou P, Anayasa M, Uney JB, Phylactou LA (2012) Down-Regulation of Myogenin Can Reverse Terminal Muscle Cell Differentiation.PLoSONE7(1):e29896.doi:10.1371/journal.pone.0029896 Editor:CarloGaetano,IstitutoDermopaticodell’Immacolata,Italy ReceivedMay20,2011;Accepte