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: Véronique Joliot, Ouardia Ait-Mohamed, Valentine Battisti, Julien Pontis, Ophélie Philipot, Philippe Robin, Hidenori Ito, Slimane Ait-Si-Ali
• Journal: PloS one (PLoS One) Vol. 9 Issue 10 Pg. e108858 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 25271443 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chromosomal Proteins, Non-Histone
• DNA-Binding Proteins
• MyoD Protein
• SMARCB1 Protein
• SMARCB1 protein, human
• Transcription Factors

Topics

• Cell Cycle Checkpoints (genetics)
• Cell Differentiation (genetics)
• Chromosomal Proteins, Non-Histone (genetics, metabolism)
• DNA-Binding Proteins (genetics, metabolism)
• HeLa Cells
• Humans
• Muscle Development (genetics)
• Muscle, Skeletal (cytology, metabolism)
• MyoD Protein (genetics, metabolism)
• SMARCB1 Protein
• Transcription Factors (genetics, metabolism)