Environmental circadian disruption re-writes liver circadian proteomes

Circadian gene expression underlies the cellular clock, but its response to environmental circadian disruption (ECD), such as shiftwork and jetlag, is ill-defined. The authors present a comprehensive comparison of male mouse liver transcriptomes, whole-cell proteomes, and nuclear proteomes under normal standard (STD) and ECD conditions. Under both conditions, post-translational control, more than transcription, primarily determines circadian functional outputs. After ECD, post-transcriptional and post-translational processes predominantly shape whole-cell and nuclear circadian proteomes, respectively. ECD re-writes the rhythmicity of 64% of the transcriptome, 98% of the whole-cell proteome, and 95% of the nuclear proteome, associated with altered cis-regulatory element enrichment, RNA processing, and protein localization. This remodeling diminishes circadian regulation of fat and carbohydrate metabolism and persists after one week of recovery.