Choi Moon-Chang, Ryu Soyoung, Hao Rui, Wang Bin, Kapur Meghan, Fan Chen-Ming, Yao Tso-Pang
Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA.
Department of Embryology, Carnegie Institution of Washington, Baltimore, MD, USA.
EMBO Rep. 2014 Nov;15(11):1175-83. doi: 10.15252/embr.201439195. Epub 2014 Sep 9.
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.
在肌肉再生过程中，转录因子Pax7刺激卫星细胞（SCs）向肌肉谱系分化，但限制脂肪生成。在此，我们确定HDAC4是Pax7依赖性肌肉再生的调节因子。在缺乏HDAC4的SCs中，Pax7及其靶基因的表达降低。我们确定HDAC4调节的Lix1是SCs增殖所需的Pax7靶基因。HDAC4失活导致SCs增殖缺陷、肌肉再生异常和脂质异常积累。此外，棕色脂肪主调节因子Prdm16及其抑制性微小RNA-133的表达也失调。因此，HDAC4是再生肌肉中Pax7依赖性SCs增殖以及潜在命运决定的新型调节因子。
