TY - JOUR
T1 - Per1/per2–igf2 axis–mediated circadian regulation of myogenic differentiation
AU - Katoku-Kikyo, Nobuko
AU - Paatela, Ellen
AU - Houtz, Daniel L.
AU - Lee, Britney
AU - Munson, Dane
AU - Wang, Xuerui
AU - Hussein, Mohammed
AU - Bhatia, Jasmeet
AU - Lim, Seunghyun
AU - Yuan, Ce
AU - Asakura, Yoko
AU - Asakura, Atsushi
AU - Kikyo, Nobuaki
N1 - Publisher Copyright:
© 2021 Katoku-Kikyo et al.
PY - 2021/7/5
Y1 - 2021/7/5
N2 - Circadian rhythms regulate cell proliferation and differentiation, but circadian control of tissue regeneration remains elusive at the molecular level. Here, we show that proper myoblast differentiation and muscle regeneration are regulated by the circadian master regulators Per1 and Per2. Depletion of Per1 or Per2 suppressed myoblast differentiation in vitro and muscle regeneration in vivo, demonstrating their nonredundant functions. Both Per1 and Per2 were required for the activation of Igf2, an autocrine promoter of myoblast differentiation, accompanied by Per-dependent recruitment of RNA polymerase II, dynamic histone modifications at the Igf2 promoter and enhancer, and the promoter–enhancer interaction. This circadian epigenetic priming created a preferred time window for initiating myoblast differentiation. Consistently, muscle regeneration was faster if initiated at night, when Per1, Per2, andIgf2 were highly expressed compared with morning. This study reveals the circadian timing as a significant factor for effective muscle cell differentiation and regeneration.
AB - Circadian rhythms regulate cell proliferation and differentiation, but circadian control of tissue regeneration remains elusive at the molecular level. Here, we show that proper myoblast differentiation and muscle regeneration are regulated by the circadian master regulators Per1 and Per2. Depletion of Per1 or Per2 suppressed myoblast differentiation in vitro and muscle regeneration in vivo, demonstrating their nonredundant functions. Both Per1 and Per2 were required for the activation of Igf2, an autocrine promoter of myoblast differentiation, accompanied by Per-dependent recruitment of RNA polymerase II, dynamic histone modifications at the Igf2 promoter and enhancer, and the promoter–enhancer interaction. This circadian epigenetic priming created a preferred time window for initiating myoblast differentiation. Consistently, muscle regeneration was faster if initiated at night, when Per1, Per2, andIgf2 were highly expressed compared with morning. This study reveals the circadian timing as a significant factor for effective muscle cell differentiation and regeneration.
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U2 - 10.1083/jcb.202101057
DO - 10.1083/jcb.202101057
M3 - Article
C2 - 34009269
AN - SCOPUS:85107085347
SN - 0021-9525
VL - 220
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 7
M1 - e202101057
ER -