Molecular architecture of the circadian clock in mammals

The circadian clock mechanism in animals involves an autoregulatory transcriptional feedback loop in which CLOCK and BMAL1 activate the transcription of the Period and Cryptochrome genes. The PERIOD and CRYPTOCHROME proteins then feed back and repress their own transcription by interaction with CLOCK and BMAL1. We have studied the biochemistry of the CLOCK:BMAL1 transcriptional activator complex using structural biology as well as the genomic targets of CLOCK and BMAL1 using ChIP-seq methods. We describe the dynamics of the core circadian clock transcriptional system. CLOCK and BMAL1 interact with the regulatory regions of thousands of genes. The gene network and dynamics of the system will be discussed. A mechanistic description of the core circadian clock mechanism should promote our understanding of how the circadian clock system influences behavior, physiology and behavioral disorders.