TABLE 3.

Summary of studies implicating CRTC1 in circadian rhythms regulation.

References	System	Findings
Sakamoto et al., 2013	C57BL/6 mice	Rhythmic expression of CRTC1 in the suprachiasmatic nucleus (SCN). CRTC1 expression was detected in the middle of the subjective day, with limited expression during early night, and late night expression levels intermediate between mid-day and early night levels. During early and late subjective night, a brief light pulse induced strong nuclear accumulation of CRTC1 in the SCN. Evidence of CRTC1-mediated Per1 gene regulation.
Jagannath et al., 2013	C57BL/6 mice	In the SCN, light-activated CRTC1 increases SIK1 levels, which in turn phosphorylate and inactivate CRTC1. This feedback mechanism limits the transcription of Per1 that promotes clock resetting. CRTC1 slows down clock-resetting and prevents an abrupt desynchrony between the master clock located in the SCN and the other peripheral clocks.
Kim et al., 2016	Drosophila	Light-independent role of Drosophila CRTC in sustaining circadian behaviors. Crtc null mutation dampens light-independent oscillations of TIMELESS (and not PERIOD) in the clock neurons.
Rossetti et al., 2017	Crtc1–/– mice	Crtc1–/– males have a hyperphagic behavior that is restricted to the diurnal (resting) phase of the light cycle during which they have a higher locomotor activity possibly due to circadian rhythms alteration.
Jagannath et al., 2021	C57BL/6 mice	Adenosine, encoding sleep history, acts upon the circadian clockwork via adenosine A1/A2A receptor signaling through the activation of the Ca2+-ERK-AP-1 and CREB/CRTC1-CRE pathways to regulate the clock genes Per1 and Per2. These signaling pathways converge upon and inhibit the same pathways activated by light. Circadian entrainment by light is thus systematically modulated on a daily basis by sleep history.