FIGURE 2.

Model of the mammalian circadian core oscillator. An activated form of BMAL1 (BMAL1*) activates the transcription of Per2 and Cry genes resulting in an increase of Per2/Cry mRNA (y1). As the levels of PER2 and CRY proteins increase, they form a complex (y2), which is transported to the nucleus. The nuclear PER2/CRY complex (y3) inhibits Per2/Cry transcription and activates Bmal1 transcription. As a result, Bmal1 mRNA (y4) and protein (y5) increase. Nuclear BMAL1 (y6) in its active form (BMAL1*, y7) restarts transcription of Per2 and Cry genes. Dashed arrows represent degradation of mRNAs and proteins. Reference parameters of the reaction kinetics are given in Table 1.