Per1/Per2-Igf2 axis-mediated circadian regulation of myogenic differentiation.

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.

Circadian Regulation in Tissue Regeneration.

Circadian rhythms regulate over 40% of protein-coding genes in at least one organ in the body through mechanisms tied to the central circadian clock and to cell-intrinsic auto-regulatory feedback loops. Distinct diurnal differences in regulation of regeneration have been found in several organs, including skin, intestinal, and hematopoietic systems. Each regenerating system contains a complex network of cell types with different circadian mechanisms contributing to regeneration.

Promotion of Myoblast Differentiation by Fkbp5 via Cdk4 Isomerization.

Fkbp5 is a widely expressed peptidyl prolyl isomerase that serves as a molecular chaperone through conformational changes of binding partners. Although it regulates diverse protein functions, little is known about its roles in myogenesis. We found here that Fkbp5 plays critical roles in myoblast differentiation through two mechanisms.

Cry2 Is Critical for Circadian Regulation of Myogenic Differentiation by Bclaf1-Mediated mRNA Stabilization of Cyclin D1 and Tmem176b.

Circadian rhythms regulate cell proliferation and differentiation; however, little is known about their roles in myogenic differentiation. Our synchronized differentiation studies demonstrate that myoblast proliferation and subsequent myotube formation by cell fusion occur in circadian manners. We found that one of the core regulators of circadian rhythms, Cry2, but not Cry1, is critical for the circadian patterns of these two critical steps in myogenic differentiation.