Circadian rhythms in physiology and behavior evolved to resonate with daily cycles in the external environment. In mammals, organs orchestrate temporal physiology over the 24-hour day, which requires extensive gene expression rhythms targeted to the right tissue. Although a core set of gene products oscillate across virtually all cell-types, gene expression profiling across tissues over the 24-hour day showed that rhythmic gene expression programs are tissue-specific. We highlight recent progress in uncovering how the circadian clock interweaves with tissue-specific gene regulatory networks involving functions such as xenobiotic metabolism, glucose homeostasis, and sleep. This progress hinges on not only comprehensive experimental approaches but also computational methods for multivariate analysis of periodic functional genomics data. This thesis first explores how circadian gene expression is regulated across tissues. Second, we investigate how dynamic chromatin interactions underlie circadian gene transcription, core clock functions, and ultimately behavior. Third, we elucidate how the temporal transcriptome in mouse cortex responds to sleep deprivation treatment. Finally, we discuss perspectives on extending the knowledge of the circadian clock in mice to human chronobiology.