Molecular feedback loops working together in the mammal's internal daily clock

In the mouse, the core mechanism for the master circadian clock involves interacting positive and negative feedback loops.

• Analysis of specific mutant mice indicates substantially altered Bmal1 rhythms.
• PERIOD2 is identified as a key positive regulator of the Bmal1 loop.
• CRYPTOCHROMES are shown to act as negative regulators for the Period and Cryptochrome cycles.
• Inhibition of CLOCK:BMAL1-mediated transcription by CRYPTOCHROME occurs through direct protein interactions, independent of other proteins.

Simplified