During muscle regeneration, the transcription factor Pax7 stimulates the differentiation of satellite cells (SCs) toward the muscle lineage but restricts adipogenesis. Here, we identify HDAC4 as a regulator of Pax7‐dependent muscle regeneration. In HDAC4‐deficient SCs, the expression of Pax7 and its target genes is reduced. We identify HDAC4‐regulated Lix1 as a Pax7 target gene required for SC proliferation. HDAC4 inactivation leads to defective SC proliferation, muscle regeneration, and aberrant lipid accumulation. Further, expression of the brown adipose master regulator Prdm16 and its inhibitory microRNA‐133 are also deregulated. Thus, HDAC4 is a novel regulator of Pax7‐dependent SC proliferation and potentially fate determination in regenerating muscle.
HDAC4 is shown to promote damage‐induced satellite cell (SC) proliferation and muscle regeneration in vivo by stimulating Pax7 expression. It also prevents aberrant lipid accumulation and induction of the brown fat transcription factor Prdm16 in regenerating muscle.
Loss of HDAC4 in SCs reduces expression of Pax7 and its target genes, which in turns inhibits SC proliferation.
Knockdown of HDAC4‐regulated Lix1, a Pax7 target, decreases the proliferative rate of SCs.
HDAC4 inactivation in SCs leads to a prominent reduction of microRNA‐133 and concomitant increase in its target, Prdm16, a master regulator of brown adipogenesis.
EMBO Reports (2014) 15: 1175–1183
- Received June 20, 2014.
- Revision received August 12, 2014.
- Accepted August 14, 2014.
- © 2014 The Authors