Rhythms of the Genome: Circadian Dynamics from Chromatin Topology, Tissue-Specific Gene Expression, to Behavior. Issue 12 (December 2018)

• Record Type: Journal Article
• Authors: Yeung, Jake; Naef, Felix
• Is Part Of: Trends in genetics. Volume 34:Issue 12(2018)
• Page Start: 915
• Page End: 926
• Publication Date: 2018-12
• Subjects: chromatin interactions -- circadian rhythms -- gene regulation -- promoter–enhancer loops -- systems chronobiology; Genetics -- Periodicals; 576.5
• DOI: 10.1016/j.tig.2018.09.005
• Languages: English
• ISSNs: 0168-9525

Abstract

Abstract : 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-h day, which requires extensive gene expression rhythms targeted to the right tissue. Although a core set of gene products oscillates across virtually all cell types, gene expression profiling across tissues over the 24-h 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. We emphasize dynamic chromatin interactions as a novel regulatory layer underlying circadian gene transcription, core clock functions, and ultimately behavior. Finally, we discuss perspectives on extending the knowledge of the circadian clock in animals to human chronobiology. Highlights: Temporal gene expression profiling across mammalian tissues showed that 24-h rhythmic transcript programs consist of a conserved core and tissue-specific gene modules. Combinations of rhythmic and tissue-specific transcription factor activities explain circadian gene expression across organs. Tissue-specific chromatin interactions enable the clock to regulate circadian gene expression. Clock-dependent chromatin interactions regulate circadian transcription and behavior. Statistical inference of internal circadian time from human healthy and diseased samples opens new prospects for circadian medicine.