Next Generation Sequencing Facilitates Quantitative Analysis of Wild Type and delta-RRE Liver Transcriptomes

In mammals, the circadian clock consists of transcriptional and translational feedback loops through DNA cis-elements such as E-box and RRE. In this study, we established mutant mice deficient for rhythmic transcription of Bmal1 gene by deleting its upstream RRE elements. We observed apparently normal circadian rhythms in the mutant, but the circadian period and amplitude of the mutants were more susceptible to disturbance of CRY1 protein rhythm. Our findings demonstrate that the RRE-mediated feedback regulation of Bmal1 underpins the E-box-mediated rhythm in cooperation with CRY1-dependent posttranslational regulation of BMAL1 protein, thereby conferring the perturbation-resistant oscillation and chronologically organized output of the circadian clock. Overall design: Circadian mRNA profiles of wild type (WT) and delta-RRE mouse liver