Fig. 1

Core clock mechanism and control of circadian muscle genes by intrinsic and extrinsic pathways. a Simplified scheme of the core clock mechanism. The clock consists of a stimulatory loop, with the CLOCK-BMAL1 heterodimer stimulating the transcription of Per and Cry genes, and an inhibitory feedback loop with the PER-CRY heterodimer translocating to the nucleus and repressing the transcription of the Clock and Bmal1 genes. An additional loop involves the ROR and RevErb factors. The different isoforms of the clock genes, including the genes coding for PER1 and PER2, CRY1 and CRY2, RORα and RORβ, and RevErbα and RevErbβ, are not indicated in the scheme. b The scheme illustrates how the master clock in the suprachiasmatic nuclei (SCN) of the hypothalamus controls motor activity and other systemic circadian rhythms (including feeding, hormone release, and body temperature), which in turn modulate the circadian rhythm of the muscle clock or directly dictate the oscillation of other muscle circadian genes. Modified from [7]