LAUSR

Significance To optimize the cellular response, cells integrate information from diverse signals. The circadian clock is an internal mechanism that anticipates environmental daily changes, relying on various inputs to estimate the time of day. Yet, little is known regarding modes of input integration by the clock. Here, we show that a combination of different signals elicits a wide range of phase response, which often cannot be readily predicted based on the response to the individual signals. Additionally, we found that the response can follow the relative change in the signal strength, suggesting the potential involvement of a fold-change detection mechanism. Our study identifies principles of input integration by the circadian clock and promotes our understanding of clock resetting.