TY - JOUR
T1 - The Nuclear Receptor and Clock Repressor Rev-erbα Suppresses Myogenesis
AU - Chatterjee, Somik
AU - Yin, Hongshan
AU - Li, Weini
AU - Lee, Jeongkyung
AU - Yechoor, Vijay K.
AU - Ma, Ke
N1 - Funding Information:
We thank the Histology Core Laboratory at Baylor College of Medicine for their expert technical assistance. We also thank Dr. Aijun Zhang, Methodist Hospital Research Institute, for help with microarray analysis. This project was supported by grants from Muscular Dystrophy Association 381294, American Heart Association 17GRNT33370012, and National Institute of Health 1R01DK112794 to K.M.; and National Institute of Health grant DK097160-01 to V.Y. K.M. as a faculty member of the City of Hope National Cancer Institute-designated Comprehensive Cancer Center is also supported by National Institute of Health award P30CA33572.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Rev-erbα is a ligand-dependent nuclear receptor and a key repressor of the molecular clock transcription network. Accumulating evidence indicate that the circadian clock machinery governs diverse biological processes in skeletal muscle, including muscle growth, repair and mass maintenance. The physiological function of Rev-erbα in myogenic regulation remains largely unknown. Here we show that Rev-erbα exerts cell-autonomous inhibitory effects on proliferation and differentiation of myogenic precursor cells, and these actions concertedly inhibit muscle regeneration in vivo. Mechanistic studies reveal Rev-erbα direct transcriptional control of two major myogenic mechanisms, proliferative pathway and the Wnt signaling cascade. Consistent with this finding, primary myoblasts lacking Rev-erbα display significantly enhanced proliferative growth and myogenic progression. Furthermore, pharmacological activation of Rev-erbα activity attenuates, whereas its inhibition by an antagonist promotes these processes. Notably, upon muscle injury, the loss-of-function of Rev-erbα in vivo augmented satellite cell proliferative expansion and regenerative progression during regeneration. Collectively, our study identifies Rev-erbα as a novel inhibitory regulator of myogenic progenitor cell properties that suppresses postnatal myogenesis. Pharmacological interventions to dampen Rev-erbα activity may have potential utilities to enhance regenerative capacity in muscle diseases.
AB - Rev-erbα is a ligand-dependent nuclear receptor and a key repressor of the molecular clock transcription network. Accumulating evidence indicate that the circadian clock machinery governs diverse biological processes in skeletal muscle, including muscle growth, repair and mass maintenance. The physiological function of Rev-erbα in myogenic regulation remains largely unknown. Here we show that Rev-erbα exerts cell-autonomous inhibitory effects on proliferation and differentiation of myogenic precursor cells, and these actions concertedly inhibit muscle regeneration in vivo. Mechanistic studies reveal Rev-erbα direct transcriptional control of two major myogenic mechanisms, proliferative pathway and the Wnt signaling cascade. Consistent with this finding, primary myoblasts lacking Rev-erbα display significantly enhanced proliferative growth and myogenic progression. Furthermore, pharmacological activation of Rev-erbα activity attenuates, whereas its inhibition by an antagonist promotes these processes. Notably, upon muscle injury, the loss-of-function of Rev-erbα in vivo augmented satellite cell proliferative expansion and regenerative progression during regeneration. Collectively, our study identifies Rev-erbα as a novel inhibitory regulator of myogenic progenitor cell properties that suppresses postnatal myogenesis. Pharmacological interventions to dampen Rev-erbα activity may have potential utilities to enhance regenerative capacity in muscle diseases.
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U2 - 10.1038/s41598-019-41059-7
DO - 10.1038/s41598-019-41059-7
M3 - Article
C2 - 30872796
AN - SCOPUS:85062936121
VL - 9
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 4585
ER -