MyoD transcription factor induces myogenesis by inhibiting Twist-1 through miR-206.
Twist-1 is mostly expressed during development and has been previously shown to control myogenesis. Because its regulation in muscle has not been fully exploited, the aim of this project was to identify micro (mi)RNAs in muscle that regulate Twist-1. miR-206, one of the most important muscle-specific miRNAs (myomiRs), was identified as a possible regulator of Twist-1 mRNA. Luciferase assays and transfections in human foetal myoblasts showed that Twist-1 is a direct target of miR-206 and that through this pathway muscle cell differentiation is promoted. We next investigated whether MyoD, a major myogenic transcription factor, regulates Twist-1 because it is known that MyoD induces expression of the miR-206 gene. We found that forced MyoD expression induced miR-206 upregulation and Twist-1 downregulation through binding to the miR-206 promoter, followed by increased muscle cell differentiation. Finally, experiments were performed in muscle cells from subjects with congenital myotonic dystrophy type 1, in which myoblasts fail to differentiate into myotubes. MyoD overexpression inhibited Twist-1 through miR-206 induction, which was followed by an increase in muscle cell differentiation. These results reveal a previously unidentified mechanism of myogenesis that might also play an important role in muscle disease.
Department of Molecular Genetics, Function & Therapy, Cyprus Institute of Neurology and Genetics, Nicosia,1683, Cyprus.
Demetris
D
Koutalianos
Department of Molecular Genetics, Function & Therapy, Cyprus Institute of Neurology and Genetics, Nicosia,1683, Cyprus.
Andrie
A
Koutsoulidou
Department of Molecular Genetics, Function & Therapy, Cyprus Institute of Neurology and Genetics, Nicosia,1683, Cyprus.
Nikilaos P
NP
Mastroyiannopoulos
Sorbonne Universités, UPMC Univ Paris 06, Centre de Recherche en Myologie, INSERM UMRS974, CNRS FRE3617, Institut de Myologie, Paris 75013, France.
Denis
D
Furling
Department of Molecular Genetics, Function & Therapy, Cyprus Institute of Neurology and Genetics, Nicosia,1683, Cyprus laphylac@cing.ac.cy.
Leonidas A
LA
Phylactou
D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D047369:Chromatin Immunoprecipitation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D024510:Muscle Development / Q000235:genetics / Q000502:physiology; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism*; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism
D035683:MicroRNAs; D017570:MyoD Protein
MiR-206; MyoD; Myogenesis; Twist-1