HDAC 4 promotes P ax7‐dependent satellite cell activation and muscle regeneration

During muscle regeneration, the transcription factor P ax7 stimulates the differentiation of satellite cells ( SC s) toward the muscle lineage but restricts adipogenesis. Here, we identify HDAC 4 as a regulator of P ax7‐dependent muscle regeneration. In HDAC 4‐deficient SC s, the expression of P ax7 and its target genes is reduced. We identify HDAC 4‐regulated Lix1 as a P ax7 target gene required for SC proliferation. HDAC 4 inactivation leads to defective SC proliferation, muscle regeneration, and aberrant lipid accumulation. Further, expression of the brown adipose master regulator P rdm16 and its inhibitory micro RNA ‐133 are also deregulated. Thus, HDAC 4 is a novel regulator of P ax7‐dependent SC proliferation and potentially fate determination in regenerating muscle.