CCAAT/Enhancer Binding Protein Beta Is Expressed in Satellite Cells and Controls Myogenesis

Upon injury, muscle satellite cells become activated and produce skeletal muscle precursors that engage in myogenesis. We demonstrate that the transcription factor CCAAT/enhancer binding protein beta (C/EBP beta) is expressed in the satellite cells of healthy muscle. C/EBP beta expression is regulated during myogenesis such that C/EBP beta is rapidly and massively downregulated upon induction to differentiate. Furthermore, persistent expression of C/EBP beta in myoblasts potently inhibits differentiation at least in part through the inhibition of MyoD protein function and stability. As a consequence, myogenic factor expression, myosin heavy chain expression, and fusogenic activity were reduced in C/EBP beta-overexpressing cells. Using knockout models, we demonstrate that loss of Cebpb expression in satellite cells results in precocious differentiation of myoblasts in growth conditions and greater cell fusion upon differentiation. In vivo, loss of Cebpb expression in satellite cells resulted in larger muscle fiber cross-sectional area and improved repair after muscle injury. Our results support the notion that C/EBP beta inhibits myogenic differentiation and that its levels must be reduced to allow for activation of MyoD target genes and the progression of differentiation. Stem Cells 2012; 30: 2619-2630