title: The pervasiveness and plasticity of circadian oscillations: the coupled circadian-oscillators framework.
abstract: BACKGROUND
  Circadian oscillations have been observed in animals, plants, fungi and cyanobacteria and play a fundamental role in coordinating the homeostasis and behavior of biological systems. Genetically encoded molecular clocks found in nearly every cell, based on negative transcription/translation feedback loops and involving only a dozen genes, play a central role in maintaining these oscillations. However, high-throughput gene expression experiments reveal that in a typical tissue, a much larger fraction ([Formula: see text]) of all transcripts oscillate with the day-night cycle and the oscillating species vary with tissue type suggesting that perhaps a much larger fraction of all transcripts, and perhaps also other molecular species, may bear the potential for circadian oscillations.
  
  
  RESULTS
  To better quantify the pervasiveness and plasticity of circadian oscillations, we conduct the first large-scale analysis aggregating the results of 18 circadian transcriptomic studies and 10 circadian metabolomic studies conducted in mice using different tissues and under different conditions. We find that over half of protein coding genes in the cell can produce transcripts that are circadian in at least one set of conditions and similarly for measured metabolites. Genetic or environmental perturbations can disrupt existing oscillations by changing their amplitudes and phases, suppressing them or giving rise to novel circadian oscillations. The oscillating species and their oscillations provide a characteristic signature of the physiological state of the corresponding cell/tissue. Molecular networks comprise many oscillator loops that have been sculpted by evolution over two trillion day-night cycles to have intrinsic circadian frequency. These oscillating loops are coupled by shared nodes in a large network of coupled circadian oscillators where the clock genes form a major hub. Cells can program and re-program their circadian repertoire through epigenetic and other mechanisms.
  
  
  METHODS
  High-resolution and tissue/condition specific circadian data and networks available at http://circadiomics.igb.uci.edu.
  
  
  BACKGROUND
  pfbaldi@ics.uci.edu
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Department of Computer Science, Institute for Genomics and Bioinformatics.
authors.forename: Vishal R
authors.initials: VR
authors.lastname: Patel
authors.affiliation: Department of Computer Science, Institute for Genomics and Bioinformatics.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Ceglia
authors.affiliation: Department of Computer Science, Institute for Genomics and Bioinformatics.
authors.forename: Michael
authors.initials: M
authors.lastname: Zeller
authors.affiliation: Department of Biological Chemistry and Center for Epigenetics and Metabolism, University of California, Irvine (UCI), Irvine, CA - 92697, USA.
authors.forename: Kristin
authors.initials: K
authors.lastname: Eckel-Mahan
authors.affiliation: Institute for Genomics and Bioinformatics, Department of Biological Chemistry and Center for Epigenetics and Metabolism, University of California, Irvine (UCI), Irvine, CA - 92697, USA.
authors.forename: Paolo
authors.initials: P
authors.lastname: Sassone-Corsi
authors.affiliation: Department of Computer Science, Institute for Genomics and Bioinformatics, Department of Biological Chemistry and Center for Epigenetics and Metabolism, University of California, Irvine (UCI), Irvine, CA - 92697, USA.
authors.forename: Pierre
authors.initials: P
authors.lastname: Baldi
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D055432:Metabolomics / Q000379:methods*; D051379:Mice; D009928:Organ Specificity; D013997:Time Factors; D059467:Transcriptome
chemical_list: D056925:Circadian Rhythm Signaling Peptides and Proteins