Abstract
Circadian information is maintained in mammalian tissues by a cell-autonomous network of transcriptional feedback loops that have evolved to optimally regulate tissue-specific functions. An analysis of daily gene expression in different tissues, as well as an evaluation of inter-tissue circadian variability, is crucial for a systems-level understanding of this transcriptional circuitry. Affymetrix gene chip measurements of liver, muscle, adipose, and lung tissues were obtained from a rich time series light/dark experiment, involving 54 normal rats sacrificed at 18 time points within the 24-hr cycle. Our analysis revealed a high degree of circadian regulation with a variable distribution of phases among the four tissues. Interestingly, only a small number of common genes maintain circadian activity in all tissues, with many of them consisting of "core-clock" components with synchronous rhythms. Our results suggest that inter-tissue circadian variability is a critical component of homeostatic body function and is mediated by diverse signaling pathways that ultimately lead to highly tissue-specific transcription regulation.