Ccndbp1 is a novel positive regulator of skeletal myogenesis

Abstract

Skeletal myogenesis is a multistep process in which basic Helix-Loop-Helix (bHLH) transcription factors like MyoD bind to E-boxes and activate downstream genes. Ccndbp1 is a HLH protein without a DNA binding region, and its function in skeletal myogenesis is unknown yet. We generated Ccndbp1-null mice by CRISPR/Cas9. Significantly, in Ccndbp1-null mice, the cross sectional area of the skeletal tibialis anterior (TA) muscle was smaller, and muscle regeneration ability and grip strength were impaired, compared with WT. This phenotype resembles myofibre hypotrophy in some human myopathies or amyoplasia. Ccndbp1 expression was up-regulated during C2C12 myogenesis. Ccndbp1 overexpression promoted myogenesis while Ccndbp1 RNAi inhibited myogenic differentiation. Co-transfection of Ccndbp1 with MyoD/E47 significantly promoted E-box-dependent transcription. Furthermore, Ccndbp1 physically associated with MyoD but not E47. These data suggested that Ccndbp1 regulates muscle differentiation via interacting with MyoD and enhancing its binding to target genes. Our study identified Ccndbp1 as a novel positive modulator of skeletal myogenic differentiation in vivo and in vitro, providing new insight to decipher the complex network involved in skeletal myogenic development and related diseases.