Figure 1. Model illustrating the core transcriptional-translational feedback loop underlying circadian rhythmicity. The components of the transcriptional activator complex, CLOCK, BMAL1, and (within SCN) NPAS2 form heterodimers that activate transcription of E-box containing genes, including the negative regulatory PER and CRY proteins. The PER-CRY protein complexes accumulate in the nucleus and block the activity of the activator complex. The alternation between the activation phase and the repression phase has a cycle length of near 24 hours. For simplicity, key events including posttranslational modifications and the generation of cascades of transcription factors leading to rhythmicity of tissue-specific “output” genes are not shown. For a more detailed model, see .