CEBPβ regulates myoblast proliferation and myogenic differentiation during human myogenesis and rescues defective differentiation in FSHD

Abstract CCAAT enhancer binding protein β (CEBPB) is a member of the bZIP transcription factor family and is expressed in many cell types. Whilst CEBPB has been shown to regulate the function of murine satellite cells, the resident skeletal muscle stem cell, however little is known of its role in human myogenesis and muscle disease. We report that CEBPB is expressed in proliferating human myoblasts but swiftly down-regulated upon myogenic differentiation. Interestingly, either over-expression or knock-down of CEBPB inhibit the proliferation rate of human myoblasts. Down-regulation of CEBPB upon myogenic differentiation is then necessary for subsequent myogenic differentiation and fusion into multinucleated myotubes. In the muscle disease context, CEBPB protein levels are increased in myoblasts derived from facioscapulohumeral muscular dystrophy (FSHD) patients. Knock-down of CEBPB in FSHD myoblasts improves myogenic differentiation. In summary, we show that CEBPB is a regulator of human myogenesis and altered CEBPB expression may contribute to defective myogenesis in FSHD.