Circadian control of global gene expression patterns.

An internal time-keeping mechanism has been observed in almost every organism studied from archaea to humans. This circadian clock provides a competitive advantage in fitness and survival ( 18, 30, 95, 129, 137 ). Researchers have uncovered the molecular composition of this internal clock by combining enzymology, molecular biology, genetics, and modeling approaches. However, understanding the mechanistic link between the clock and output responses has been elusive. In three model organisms, Arabidopsis thaliana, Drosophila melanogaster, and Mus musculus, whole-genome expression arrays have enabled researchers to investigate how maintaining a time-keeping mechanism connects to an adaptive advantage. Here, we review the impacts transcriptomics have had on our understanding of the clock and how this molecular clock connects with system-level circadian responses. We explore the discoveries made possible by high-throughput RNA assays, the network approaches used to investigate these large transcript datasets, and potential future directions.

[1]  R. Green,et al.  CIRCADIAN CLOCK ASSOCIATED1 Transcript Stability and the Entrainment of the Circadian Clock in Arabidopsis1[W][OA] , 2007, Plant Physiology.

[2]  B. H. Miller,et al.  Coordinated Transcription of Key Pathways in the Mouse by the Circadian Clock , 2002, Cell.

[3]  Carl Hirschie Johnson,et al.  The Adaptive Value of Circadian Clocks An Experimental Assessment in Cyanobacteria , 2004, Current Biology.

[4]  S. Golden,et al.  How a cyanobacterium tells time. , 2008, Current opinion in microbiology.

[5]  Jon W. Huss,et al.  BioGPS: an extensible and customizable portal for querying and organizing gene annotation resources , 2009, Genome Biology.

[6]  Xiang-Sun Zhang,et al.  A network biology study on circadian rhythm by integrating various omics data. , 2009, Omics : a journal of integrative biology.

[7]  Padhraic Smyth,et al.  Bayesian detection of non-sinusoidal periodic patterns in circadian expression data , 2009, Bioinform..

[8]  S. Kay,et al.  Genome-Wide Expression Analysis in DrosophilaReveals Genes Controlling Circadian Behavior , 2002, The Journal of Neuroscience.

[9]  T. Roenneberg,et al.  Modelling Biological Rhythms , 2008, Current Biology.

[10]  U. Schibler,et al.  Regulation of circadian gene expression in liver by systemic signals and hepatocyte oscillators. , 2007, Cold Spring Harbor symposia on quantitative biology.

[11]  Joseph S. Takahashi,et al.  The Meter of Metabolism , 2008, Cell.

[12]  Xun Gu,et al.  Comparative analyses reveal distinct sets of lineage-specific genes within Arabidopsis thaliana , 2010, BMC Evolutionary Biology.

[13]  C. L. Baker,et al.  Post-translational modifications in circadian rhythms. , 2009, Trends in biochemical sciences.

[14]  T. Mizuno,et al.  Cell autonomous circadian waves of the APRR1/TOC1 quintet in an established cell line of Arabidopsis thaliana. , 2003, Plant & cell physiology.

[15]  Andrew I. Su,et al.  A Genome-wide RNAi Screen for Modifiers of the Circadian Clock in Human Cells , 2009, Cell.

[16]  Matthew E. Hudson,et al.  Identification of Promoter Motifs Involved in the Network of Phytochrome A-Regulated Gene Expression by Combined Analysis of Genomic Sequence and Microarray Data1[w] , 2003, Plant Physiology.

[17]  Ilya Shmulevich,et al.  Robust regression for periodicity detection in non-uniformly sampled time-course gene expression data , 2007, BMC Bioinformatics.

[18]  M. W. Young,et al.  Posttranscriptional and Posttranslational Regulation of Clock Genes , 2004, Journal of biological rhythms.

[19]  Catharine E. Boothroyd,et al.  The In(put)s and Out(put)s of the Drosophila Circadian Clock , 2008, Annals of the New York Academy of Sciences.

[20]  Jennifer J. Loros,et al.  Circadian Programs of Transcriptional Activation, Signaling, and Protein Turnover Revealed by Microarray Analysis of Mammalian Cells , 2002, Current Biology.

[21]  Andrey A. Ptitsyn,et al.  Digital Signal Processing Reveals Circadian Baseline Oscillation in Majority of Mammalian Genes , 2007, PLoS Comput. Biol..

[22]  Anthony Hall,et al.  Plant Circadian Clocks Increase Photosynthesis, Growth, Survival, and Competitive Advantage , 2005, Science.

[23]  C. Kyriacou,et al.  Comparative analysis of circadian clock genes in insects , 2008, Insect molecular biology.

[24]  Fiona C. Robertson,et al.  Interactions between circadian and hormonal signalling in plants , 2009, Plant Molecular Biology.

[25]  P. Más,et al.  Time for circadian rhythms: plants get synchronized. , 2009, Current opinion in plant biology.

[26]  P. Etter,et al.  The ups and downs of daily life: profiling circadian gene expression in Drosophila. , 2002, BioEssays : news and reviews in molecular, cellular and developmental biology.

[27]  Peer Bork,et al.  Comparison of computational methods for the identification of cell cycle-regulated genes , 2005, Bioinform..

[28]  Michael Brunner,et al.  Interlocked feedback loops of the circadian clock of Neurospora crassa , 2008, Molecular microbiology.

[29]  Joanne Chory,et al.  A Morning-Specific Phytohormone Gene Expression Program underlying Rhythmic Plant Growth , 2008, PLoS biology.

[30]  T. Mizuno,et al.  Comparative transcriptome of diurnally oscillating genes and hormone-responsive genes in Arabidopsis thaliana: insight into circadian clock-controlled daily responses to common ambient stresses in plants. , 2008, Plant & cell physiology.

[31]  Leonid Kruglyak,et al.  Identification and Dissection of a Complex DNA Repair Sensitivity Phenotype in Baker's Yeast , 2008, PLoS genetics.

[32]  Rachel B. Brem,et al.  The landscape of genetic complexity across 5,700 gene expression traits in yeast. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[33]  R. W. Padgett,et al.  Circadian regulation of a limited set of conserved microRNAs in Drosophila , 2008, BMC Genomics.

[34]  Jeffrey C. Hall,et al.  CYCLE Is a Second bHLH-PAS Clock Protein Essential for Circadian Rhythmicity and Transcription of Drosophila period and timeless , 1998, Cell.

[35]  M. Gho,et al.  Laser Microdissection of Sensory Organ Precursor Cells of Drosophila Microchaetes , 2010, PloS one.

[36]  Susumu Goto,et al.  KEGG: Kyoto Encyclopedia of Genes and Genomes , 2000, Nucleic Acids Res..

[37]  C. R. McClung,et al.  Phase-Specific Circadian Clock Regulatory Elements in Arabidopsis1 , 2002, Plant Physiology.

[38]  Satchidananda Panda,et al.  Harmonics of Circadian Gene Transcription in Mammals , 2009, PLoS genetics.

[39]  Andrey A. Ptitsyn,et al.  Comprehensive analysis of circadian periodic pattern in plant transcriptome , 2008, BMC Bioinformatics.

[40]  Timothy Nelson,et al.  Laser microdissection of plant tissue: what you see is what you get. , 2006, Annual review of plant biology.

[41]  S. Kay,et al.  DNA Arrays: Applications and Implications for Circadian Biology , 2003, Journal of biological rhythms.

[42]  Yuting Liu,et al.  Analysis of Gene Regulatory Networks in the Mammalian Circadian Rhythm , 2008, PLoS Comput. Biol..

[43]  D. P. King,et al.  Molecular genetics of circadian rhythms in mammals. , 2000, Annual review of neuroscience.

[44]  Xiaodong Wang,et al.  Robust discovery of periodically expressed genes using the laplace periodogram , 2009, BMC Bioinformatics.

[45]  Jie Chen,et al.  Bioinformatics Original Paper Detecting Periodic Patterns in Unevenly Spaced Gene Expression Time Series Using Lomb–scargle Periodograms , 2022 .

[46]  P. Benfey,et al.  High-Throughput RNA Isolation Technologies. New Tools for High-Resolution Gene Expression Profiling in Plant Systems1 , 2005, Plant Physiology.

[47]  D. Valle,et al.  MicroRNA (miRNA) Transcriptome of Mouse Retina and Identification of a Sensory Organ-specific miRNA Cluster* , 2007, Journal of Biological Chemistry.

[48]  Yi Liu,et al.  The Neurospora crassa circadian clock. , 2007, Advances in genetics.

[49]  C. Green,et al.  Posttranscriptional regulation of mammalian circadian clock output. , 2007, Cold Spring Harbor symposia on quantitative biology.

[50]  Kathryn S. Lilley,et al.  Circadian Orchestration of the Hepatic Proteome , 2006, Current Biology.

[51]  Brad T. Sherman,et al.  Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists , 2008, Nucleic acids research.

[52]  C A Fuller,et al.  Neurospora circadian rhythms in space: a reexamination of the endogenous-exogenous question. , 1984, Science.

[53]  A. Sehgal,et al.  Probing the Relative Importance of Molecular Oscillations in the Circadian Clock , 2008, Genetics.

[54]  C S Pittendrigh,et al.  Temporal organization: reflections of a Darwinian clock-watcher. , 1993, Annual review of physiology.

[55]  Ronald K. Pearson,et al.  BMC Bioinformatics BioMed Central Methodology article , 2005 .

[56]  Felix Naef,et al.  Modeling an Evolutionary Conserved Circadian Cis-Element , 2008, PLoS Comput. Biol..

[57]  G. E. Duffield,et al.  DNA Microarray Analyses of Circadian Timing: The Genomic Basis of Biological Time , 2003, Journal of neuroendocrinology.

[58]  C. R. McClung,et al.  Comes a time. , 2008, Current opinion in plant biology.

[59]  Terence P. Speed,et al.  On Gene Ranking Using Replicated Microarray Time Course Data , 2009, Biometrics.

[60]  E. Tobin,et al.  Testing Time: Can Ethanol-Induced Pulses of Proposed Oscillator Components Phase Shift Rhythms in Arabidopsis? , 2008, Journal of biological rhythms.

[61]  R. Green,et al.  Evidence for the adaptive significance of circadian rhythms. , 2009, Ecology letters.

[62]  Andrey A. Ptitsyn,et al.  Permutation test for periodicity in short time series data , 2006, BMC Bioinformatics.

[63]  P. Benfey,et al.  Root layers: complex regulation of developmental patterning. , 2008, Current opinion in genetics & development.

[64]  P. Taghert,et al.  Organization of the Drosophila Circadian Control Circuit , 2008, Current Biology.

[65]  Takeya Kasukawa,et al.  Proof-by-synthesis of the transcriptional logic of mammalian circadian clocks , 2008, Nature Cell Biology.

[66]  T. Imaizumi,et al.  Arabidopsis circadian clock and photoperiodism: time to think about location. , 2010, Current opinion in plant biology.

[67]  Michael F. Covington,et al.  Global transcriptome analysis reveals circadian regulation of key pathways in plant growth and development , 2008, Genome Biology.

[68]  P. Hardin Transcription Regulation within the Circadian Clock: The E-box and Beyond , 2004, Journal of biological rhythms.

[69]  Kiyoko F. Aoki-Kinoshita,et al.  From genomics to chemical genomics: new developments in KEGG , 2005, Nucleic Acids Res..

[70]  A. Millar,et al.  Circadian dysfunction causes aberrant hypocotyl elongation patterns in Arabidopsis. , 1999, The Plant journal : for cell and molecular biology.

[71]  Hongzhe Li,et al.  Model-based methods for identifying periodically expressed genes based on time course microarray gene expression data , 2004, Bioinform..

[72]  P. Hardin,et al.  Circadian oscillators of Drosophila and mammals , 2006, Journal of Cell Science.

[73]  C. R. McClung,et al.  Enhanced Fitness Conferred by Naturally Occurring Variation in the Circadian Clock , 2003, Science.

[74]  Andrey A. Ptitsyn,et al.  Analysis of circadian pattern reveals tissue-specific alternative transcription in leptin signaling pathway , 2007, BMC Bioinformatics.

[75]  Henry D. Priest,et al.  Cis-regulatory elements in plant cell signaling. , 2009, Current opinion in plant biology.

[76]  M. Ashburner,et al.  Gene Ontology: tool for the unification of biology , 2000, Nature Genetics.

[77]  S. Nelson,et al.  Dissecting differential gene expression within the circadian neuronal circuit of Drosophila , 2010, Nature Neuroscience.

[78]  Kai-Florian Storch,et al.  Physiological significance of a peripheral tissue circadian clock , 2008, Proceedings of the National Academy of Sciences.

[79]  C. R. McClung Circadian rhythms in plants: a millennial view , 2000 .

[80]  Hiroki R Ueda,et al.  Analysis and synthesis of high-amplitude Cis-elements in the mammalian circadian clock , 2008, Proceedings of the National Academy of Sciences.

[81]  Jana Husse,et al.  A time to fast, a time to feast: The crosstalk between metabolism and the circadian clock , 2009, Molecules and cells.

[82]  S. Golden,et al.  Resonating circadian clocks enhance fitness in cyanobacteria. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[83]  S. Harmer,et al.  The circadian system in higher plants. , 2009, Annual review of plant biology.

[84]  Stacey L. Harmer,et al.  Rhythmic growth explained by coincidence between internal and external cues , 2007, Nature.

[85]  Gregory M. Cahill,et al.  Clock mechanisms in zebrafish , 2002, Cell and Tissue Research.

[86]  M. Hastings,et al.  Circadian Clocks: Timely Interference by MicroRNAs , 2007, Current Biology.

[87]  V. Cassone,et al.  Circadian profiling of the transcriptome in NIH/3T3 fibroblasts: comparison with rhythmic gene expression in SCN2.2 cells and the rat SCN. , 2007, Physiological genomics.

[88]  Ghislain Breton,et al.  A Functional Genomics Approach Reveals CHE as a Component of the Arabidopsis Circadian Clock , 2009, Science.

[89]  M. Gouy,et al.  Date of the monocot-dicot divergence estimated from chloroplast DNA sequence data. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[90]  S. Panda,et al.  Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression , 2009, Proceedings of the National Academy of Sciences.

[91]  L. Kruglyak,et al.  Genetic Dissection of Transcriptional Regulation in Budding Yeast , 2002, Science.

[92]  Connor W. McEntee,et al.  Network Discovery Pipeline Elucidates Conserved Time-of-Day–Specific cis-Regulatory Modules , 2007, PLoS genetics.

[93]  H. Wijnen,et al.  Integration of Light and Temperature in the Regulation of Circadian Gene Expression in Drosophila , 2007, PLoS genetics.

[94]  Zhaohui S. Qin,et al.  Statistical resynchronization and Bayesian detection of periodically expressed genes. , 2004, Nucleic acids research.

[95]  Daily Watch on Metabolism , 2007, Science.

[96]  Janet M Thornton,et al.  A bioinformatician's view of the metabolome. , 2006, BioEssays : news and reviews in molecular, cellular and developmental biology.

[97]  J. Takahashi,et al.  Molecular components of the mammalian circadian clock. , 2006, Human molecular genetics.

[98]  A. Matsumoto Genome-wide screenings for circadian clock genes in Drosophila , 2005 .

[99]  T. Mizuno,et al.  PSEUDO-RESPONSE REGULATORS 9, 7, and 5 Are Transcriptional Repressors in the Arabidopsis Circadian Clock[W][OA] , 2010, Plant Cell.

[100]  Masamitsu Iino,et al.  System-level identification of transcriptional circuits underlying mammalian circadian clocks , 2005, Nature Genetics.

[101]  S. Golden,et al.  Winding up the cyanobacterial circadian clock. , 2007, Trends in microbiology.

[102]  R. Macknight,et al.  Be more specific! Laser-assisted microdissection of plant cells. , 2005, Trends in plant science.

[103]  Rolf Apweiler,et al.  Linking publication, gene and protein data , 2006, Nature Cell Biology.

[104]  C Robertson McClung,et al.  Two Arabidopsis circadian oscillators can be distinguished by differential temperature sensitivity , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[105]  E. Tobin,et al.  Circadian Rhythms Confer a Higher Level of Fitness to Arabidopsis Plants1 , 2002, Plant Physiology.

[106]  Kevin P. Keegan,et al.  Meta-Analysis of Drosophila Circadian Microarray Studies Identifies a Novel Set of Rhythmically Expressed Genes , 2007, PLoS Comput. Biol..

[107]  H. Ueda,et al.  Genome-wide Transcriptional Orchestration of Circadian Rhythms inDrosophila * 210 , 2002, The Journal of Biological Chemistry.

[108]  Jose L Pruneda-Paz,et al.  LUX ARRHYTHMO encodes a Myb domain protein essential for circadian rhythms. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[109]  Haruhiko Soma,et al.  A direct repeat of E-box-like elements is required for cell-autonomous circadian rhythm of clock genes , 2008, BMC Molecular Biology.

[110]  Satchidananda Panda,et al.  Circadian transcriptional output in the SCN and liver of the mouse. , 2003, Novartis Foundation symposium.

[111]  Ciaran L. Kelly,et al.  The Circadian Clock in Arabidopsis Roots Is a Simplified Slave Version of the Clock in Shoots , 2008, Science.

[112]  Edward R. Dougherty,et al.  Identifying Genes Involved in Cyclic Processes by Combining Gene Expression Analysis and Prior Knowledge , 2009, EURASIP J. Bioinform. Syst. Biol..

[113]  K. Obrietan,et al.  Revealing a Role of MicroRNAs in the Regulation of the Biological Clock , 2007, Cell cycle.

[114]  R. Green,et al.  Regulation of output from the plant circadian clock , 2007, The FEBS journal.

[115]  Kai-Florian Storch,et al.  Extensive and divergent circadian gene expression in liver and heart , 2002, Nature.

[116]  Michael F. Covington,et al.  The Circadian Clock Regulates Auxin Signaling and Responses in Arabidopsis , 2007, PLoS biology.

[117]  Jason A. Papin,et al.  Applications of genome-scale metabolic reconstructions , 2009, Molecular systems biology.

[118]  C. Robertson McClung,et al.  Plant Circadian Rhythms , 2006, The Plant Cell Online.

[119]  S. Kay,et al.  Orchestrated transcription of key pathways in Arabidopsis by the circadian clock. , 2000, Science.

[120]  B. Staels,et al.  Rev-erb-α: an integrator of circadian rhythms and metabolism , 2009 .

[121]  B. Palsson,et al.  Metabolic systems biology , 2009, Encyclopedia of Complexity and Systems Science.

[122]  StrimmerKorbinian,et al.  Identifying periodically expressed transcripts in microarray time series data , 2004 .

[123]  R. Mott,et al.  The 1001 Genomes Project for Arabidopsis thaliana , 2009, Genome Biology.

[124]  J. Dunlap,et al.  Role for antisense RNA in regulating circadian clock function in Neurospora crassa , 2003, Nature.

[125]  S. Kay,et al.  Exploring the transcriptional landscape of plant circadian rhythms using genome tiling arrays , 2009, Genome Biology.

[126]  Neil Dalchau,et al.  Modulation of environmental responses of plants by circadian clocks. , 2007, Plant, cell & environment.

[127]  S. Kay,et al.  Positive and Negative Factors Confer Phase-Specific Circadian Regulation of Transcription in Arabidopsisw⃞ , 2005, The Plant Cell Online.

[128]  Jay C Dunlap,et al.  The Neurospora Circadian System , 2004, Journal of biological rhythms.

[129]  Korbinian Strimmer,et al.  Identifying periodically expressed transcripts in microarray time series data , 2008, Bioinform..

[130]  Yoshihiro Yamanishi,et al.  KEGG for linking genomes to life and the environment , 2007, Nucleic Acids Res..

[131]  Nicholas J Provart,et al.  Genotype and time of day shape the Populus drought response. , 2009, The Plant journal : for cell and molecular biology.

[132]  Connor W. McEntee,et al.  The DIURNAL project: DIURNAL and circadian expression profiling, model-based pattern matching, and promoter analysis. , 2007, Cold Spring Harbor symposia on quantitative biology.

[133]  C. R. McClung,et al.  Enhancer Trapping Reveals Widespread Circadian Clock Transcriptional Control in Arabidopsis1[w] , 2003, Plant Physiology.

[134]  I. Simon,et al.  Combined analysis reveals a core set of cycling genes , 2007, Genome Biology.

[135]  V. Laudet,et al.  Circadian Regulation of Diverse Gene Products Revealed by mRNA Expression Profiling of Synchronized Fibroblasts* 210 , 2001, The Journal of Biological Chemistry.

[136]  Jorge Gonçalves,et al.  The Arabidopsis Circadian Clock Incorporates a cADPR-Based Feedback Loop , 2007, Science.

[137]  Michael Ruogu Zhang,et al.  Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. , 1998, Molecular biology of the cell.

[138]  S. Kay,et al.  Time zones: a comparative genetics of circadian clocks , 2001, Nature Reviews Genetics.

[139]  David K Welsh,et al.  Bioluminescence imaging in living organisms. , 2005, Current opinion in biotechnology.

[140]  A. Hall,et al.  Functional independence of circadian clocks that regulate plant gene expression , 2000, Current Biology.

[141]  S. Kay,et al.  An expanding universe of circadian networks in higher plants. , 2010, Trends in plant science.

[142]  Martin Straume,et al.  DNA Microarray Time Series Analysis: Automated Statistical Assessment of Circadian Rhythms in Gene Expression Patterning , 2004, Numerical Computer Methods, Part D.