Figure 1.

A typical circadian clockwork involved in mammalian cells. It consists of two clockworks, the primary and the secondary TTFLs. A set of core clock genes in those two TTFLs are essential for producing the 24-h self-sustained indigenous oscillations. The primary TTFL composed of CLOCK, BMAL1, CRY, and PER. The CLOCK:BMAL1 heterodimer induces the clock-controlled genes and CRY and PER act as negative regulators for their own transcriptions. In the secondary TTFL, the Rev-Erbα and RORα are induced by the CLOCK:BMAL1. Their product RORα counteracts with the primary clock genes.