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 feedback and repress their own transcription by interaction with CLOCK and BMAL1. Recently, we have focused on the biochemical mechanisms of the core circadian transcriptional regulators and have used structural biology and genomics to study the CLOCK:BMAL1 complex and its genomic targets. Using x-ray crystallography, we have solved the three-dimensional structure of the CLOCK:BMAL1 heterodimeric complex. In addition, we have interrogated on a genome-wide level the cis-acting regulatory elements (cistrome) of the entire CLOCK:BMAL1 transcriptional feedback loop. This has revealed a global circadian regulation of transcription factor occupancy, RNA polymerase II recruitment and initiation, nascent transcription and chromatin remodelling. In addition, we have used cell-based circadian rhythms to screen for small molecules that perturb the clock system.

Transcriptional architecture of the circadian clock in mammals

246th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.