Mammals evolved an endogenous timing system to coordinate their physiology and
behaviour to the 24h period of the solar day. While it is well accepted that
circadian rhythms are generated by intracellular transcriptional feedback
loops, it is still debated which network motifs are necessary and sufficient
for generating self-sustained oscillations. Here, we systematically explore a
data-based circadian oscillator model with multiple negative and positive
feedback loops and identify a series of three subsequent inhibitions known as
“repressilator” as a core element of the mammalian circadian oscillator. The
central role of the repressilator motif is consistent with time-resolved ChIP-
seq experiments of circadian clock transcription factors and loss of
rhythmicity in core clock gene knockouts
