title: HDAC4 promotes Pax7-dependent satellite cell activation and muscle regeneration.
abstract: 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.
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA.
authors.forename: Moon-Chang
authors.initials: MC
authors.lastname: Choi
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA.
authors.forename: Soyoung
authors.initials: S
authors.lastname: Ryu
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Hao
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA.
authors.forename: Meghan
authors.initials: M
authors.lastname: Kapur
authors.affiliation: Department of Embryology, Carnegie Institution of Washington, Baltimore, MD, USA.
authors.forename: Chen-Ming
authors.initials: CM
authors.lastname: Fan
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA tsopang.yao@duke.edu.
authors.forename: Tso-Pang
authors.initials: TP
authors.lastname: Yao
mesh_terms: D000818:Animals; D000071183:Autophagy-Related Proteins; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D051763:PAX7 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012038:Regeneration; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism* / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000071183:Autophagy-Related Proteins; D004268:DNA-Binding Proteins; C499180:Lix1 protein, mouse; D035683:MicroRNAs; C517732:Mirn133 microRNA, mouse; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse; C521133:Prdm16 protein, mouse; D011506:Proteins; D014157:Transcription Factors; C498618:Hdac5 protein, mouse; D006655:Histone Deacetylases
keywords: HDAC4; Pax7; muscle regeneration