TY - JOUR T1 - Circadian timing-dependent myoblast differentiation and muscle regeneration JF - bioRxiv DO - 10.1101/2020.07.29.209312 SP - 2020.07.29.209312 AU - Nobuko Katoku-Kikyo AU - Ellen Paatela AU - Daniel L. Houtz AU - Britney Lee AU - Dane Munson AU - Xuerui Wang AU - Mohammed Hussein AU - Jasmeet Bhatia AU - Seunghyun Lim AU - Ce Yuan AU - Yoko Asakura AU - Atsushi Asakura AU - Nobuaki Kikyo Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/07/30/2020.07.29.209312.abstract N2 - Circadian rhythms regulate cell proliferation and differentiation but circadian control of tissue regeneration remains elusive at the molecular level. Here, we show that the circadian master regulators Per1 and Per2 are integral components defining the efficiency of myoblast differentiation and muscle regeneration. We found that the depletion of Per1 or Per2 suppressed myoblast differentiation in vitro and muscle regeneration in vivo, demonstrating their non-redundant functions. Both Per1 and Per2 directly activated 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 oscillation created a preferred time window for initiating myoblast differentiation. Consistently, muscle regeneration was faster if initiated at night when Per1, Per2, and Igf2 were highly expressed compared with morning. This study reveals the circadian timing as a significant factor for effective muscle cell differentiation and regeneration.Competing Interest StatementThe authors have declared no competing interest. ER -