Differentiation of myoblasts is essential in the development and regeneration of skeletal muscles to form multinucleated, contractile muscle fibers. However, the process of myoblast differentiation in mammals is complicated and requires to be further investigated. In this study, we found Palmdelphin (Palmd), a cytosolic protein, promotes myoblast differentiation. Palmd is predominantly expressed in the cytosol of myoblasts and is gradually up-regulated after differentiation. Knockdown of Palmd by small interfering RNA (siRNA) in C2C12 markedly inhibits myogenic differentiation, suggesting a specific role of Palmd in the morphological changes of myoblast differentiation program. Overexpression of Palmd in C2C12 enhances myogenic differentiation. Remarkably, inhibition of Palmd results in impaired myotube formation during muscle regeneration after injury. These findings reveal a new cytosolic protein that promotes mammalian myoblast differentiation and provide new insights into the molecular regulation of muscle formation.
Objectives Mixed lineage leukaemia protein‐1 (MLL1) mediates histone 3 lysine 4 (H3K4) trimethylation (me3) and plays vital roles during early embryonic development and hematopoiesis. In our previous study, we found its expression was positively correlated with embryonic myogenic ability in pigs, indicating its potential roles in mammalian muscle development. The present work aimed to explore the roles and regulation mechanisms of MLL1 in myogenesis. Materials and methods The expression of MLL1 in C2C12 cells was experimentally manipulated using small interfering RNAs (siRNA). 5‐ethynyl‐2′‐deoxyuridine (EdU) assay, cell cycle assay, immunofluorescence, qRT‐PCR and Western blot were performed to assess myoblast proliferation and differentiation. Chromatin immunoprecipitation assay was conducted to detect H3K4me3 enrichment on myogenic factor 5 (Myf5) promoter. A cardiotoxin (CTX)‐mediated muscle regeneration model was used to investigate the effects of MLL1 on myogenesis in vivo. Results MLL1 was highly expressed in proliferating C2C12 cells, and expression decreased after differentiation. Knocking down MLL1 suppressed myoblast proliferation and impaired myoblast differentiation. Furthermore, knockdown of MLL1 resulted in the arrest of cell cycle in G1 phase, with decreased expressions of Myf5 and Cyclin D1. Mechanically, MLL1 transcriptionally regulated Myf5 by mediating H3K4me3 on its promoter. In vivo data implied that MLL1 was required for Pax7‐positive satellite cell proliferation and muscle repair. Conclusion MLL1 facilitates proliferation of myoblasts and Pax7‐positive satellite cells by epigenetically regulating Myf5 via mediating H3K4me3 on its promoter.
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