title: The SWI/SNF subunit/tumor suppressor BAF47/INI1 is essential in cell cycle arrest upon skeletal muscle terminal differentiation.
abstract: Myogenic terminal differentiation is a well-orchestrated process starting with permanent cell cycle exit followed by muscle-specific genetic program activation. Individual SWI/SNF components have been involved in muscle differentiation. Here, we show that the master myogenic differentiation factor MyoD interacts with more than one SWI/SNF subunit, including the catalytic subunit BRG1, BAF53a and the tumor suppressor BAF47/INI1. Downregulation of each of these SWI/SNF subunits inhibits skeletal muscle terminal differentiation but, interestingly, at different differentiation steps and extents. BAF53a downregulation inhibits myotube formation but not the expression of early muscle-specific genes. BRG1 or BAF47 downregulation disrupt both proliferation and differentiation genetic programs expression. Interestingly, BRG1 and BAF47 are part of the SWI/SNF remodeling complex as well as the N-CoR-1 repressor complex in proliferating myoblasts. However, our data show that, upon myogenic differentiation, BAF47 shifts in favor of N-CoR-1 complex. Finally, BRG1 and BAF47 are well-known tumor suppressors but, strikingly, only BAF47 seems essential in the myoblasts irreversible cell cycle exit. Together, our data unravel differential roles for SWI/SNF subunits in muscle differentiation, with BAF47 playing a dual role both in the permanent cell cycle exit and in the regulation of muscle-specific genes.
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Centre Epigénétique et Destin Cellulaire, UMR7216, Centre National de la Recherche Scientifique CNRS, Université Paris Diderot, Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Joliot
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Centre Epigénétique et Destin Cellulaire, UMR7216, Centre National de la Recherche Scientifique CNRS, Université Paris Diderot, Paris, France.
authors.forename: Ouardia
authors.initials: O
authors.lastname: Ait-Mohamed
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Centre Epigénétique et Destin Cellulaire, UMR7216, Centre National de la Recherche Scientifique CNRS, Université Paris Diderot, Paris, France.
authors.forename: Valentine
authors.initials: V
authors.lastname: Battisti
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Centre Epigénétique et Destin Cellulaire, UMR7216, Centre National de la Recherche Scientifique CNRS, Université Paris Diderot, Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Pontis
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Centre Epigénétique et Destin Cellulaire, UMR7216, Centre National de la Recherche Scientifique CNRS, Université Paris Diderot, Paris, France.
authors.forename: Ophélie
authors.initials: O
authors.lastname: Philipot
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Centre Epigénétique et Destin Cellulaire, UMR7216, Centre National de la Recherche Scientifique CNRS, Université Paris Diderot, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Robin
authors.affiliation: Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Human Service Center, Aichi, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ito
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Centre Epigénétique et Destin Cellulaire, UMR7216, Centre National de la Recherche Scientifique CNRS, Université Paris Diderot, Paris, France.
authors.forename: Slimane
authors.initials: S
authors.lastname: Ait-Si-Ali
mesh_terms: D059447:Cell Cycle Checkpoints / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D024510:Muscle Development / Q000235:genetics*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D000071796:SMARCB1 Protein; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D017570:MyoD Protein; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors