Cellular and Molecular Life Sciences

, Volume 73, Issue 3, pp 497–521 | Cite as

Circadian mRNA expression: insights from modeling and transcriptomics



Circadian clocks synchronize organisms to the 24 h rhythms of the environment. These clocks persist under constant conditions, have their origin at the cellular level, and produce an output of rhythmic mRNA expression affecting thousands of transcripts in many mammalian cell types. Here, we review the charting of circadian output rhythms in mRNA expression, focusing on mammals. We emphasize the challenges in statistics, interpretation, and quantitative descriptions that such investigations have faced and continue to face, and outline remaining outstanding questions.


Circadian mRNA expression Post-transcriptional regulation Systems biology Biostatistics 

Supplementary material

18_2015_2072_MOESM1_ESM.xlsx (7 kb)
Supplementary material 1 (XLSX 7 kb)
18_2015_2072_MOESM2_ESM.nb (200 kb)
Supplementary material 2 (NB 201 kb)


  1. 1.
    Eskin A (1979) Identification and physiology of circadian pacemakers. Introduction. Fed Proc 38:2570–2572PubMedGoogle Scholar
  2. 2.
    Takahashi JS, Zatz M (1982) Regulation of circadian rhythmicity. Science 217:1104–1111. doi:10.1126/science.6287576 CrossRefPubMedGoogle Scholar
  3. 3.
    Pittendrigh CS (1965) Biological clocks, the functions, ancient and modern, of biological oscillations. In: Sci. Sixties Proc. 1965 Cloudcroft Symp. Air Force Office of Scientific Research, Arlington, VA., pp 96–111Google Scholar
  4. 4.
    Hamner KC, Finn JC, Sirohi GS, Hoshizaki T, Carpenter BH (1962) The biological clock at the south pole. Nature 195:476–480. doi:10.1038/195476a0 CrossRefGoogle Scholar
  5. 5.
    Tauber E, Last KS, Olive PJW, Kyriacou CP (2004) Clock gene evolution and functional divergence. J Biol Rhythms 19:445–458. doi:10.1177/0748730404268775 CrossRefPubMedGoogle Scholar
  6. 6.
    Golden SS, Canales SR (2003) Cyanobacterial circadian clocks— timing is everything. Nat Rev Microbiol 1:191–199. doi:10.1038/nrmicro774 CrossRefPubMedGoogle Scholar
  7. 7.
    Dong G, Kim Y-I, Golden SS (2010) Simplicity and complexity in the cyanobacterial circadian clock mechanism. Curr Opin Genet Dev 20:619–625. doi:10.1016/j.gde.2010.09.002 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Pittendrigh CS (1993) Temporal organization: reflections of a Darwinian clock-watcher. Annu Rev Physiol 55:16–54. doi:10.1146/annurev.ph.55.030193.000313 CrossRefPubMedGoogle Scholar
  9. 9.
    Rosbash M (2009) The implications of multiple circadian clock origins. PLoS Biol 7:e1000062. doi:10.1371/journal.pbio.1000062 CrossRefPubMedCentralGoogle Scholar
  10. 10.
    Gehring W, Rosbash M (2003) The coevolution of blue-light photoreception and circadian rhythms. J Mol Evol 57:S286–S289. doi:10.1007/s00239-003-0038-8 CrossRefPubMedGoogle Scholar
  11. 11.
    Sancar A, Lindsey-Boltz LA, Kang T-H, Reardon JT, Lee JH, Ozturk N (2010) Circadian clock control of the cellular response to DNA damage. FEBS Lett 584:2618–2625. doi:10.1016/j.febslet.2010.03.017 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Johnson CH (2010) Circadian clocks and cell division. Cell Cycle 9:3864–3873. doi:10.4161/cc.9.19.13205 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Hardin PE, Hall JC, Rosbash M (1990) Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels. Nature 343:536–540. doi:10.1038/343536a0 CrossRefPubMedGoogle Scholar
  14. 14.
    Aronson BD, Johnson KA, Loros JJ, Dunlap JC (1994) Negative feedback defining a circadian clock: autoregulation of the clock gene frequency. Science 263:1578–1584. doi:10.1126/science.8128244 CrossRefPubMedGoogle Scholar
  15. 15.
    Dunlap JC (1999) Molecular bases for circadian clocks review. Cell 96:271–290CrossRefPubMedGoogle Scholar
  16. 16.
    Hsu PY, Harmer SL (2014) Wheels within wheels: the plant circadian system. Trends Plant Sci 19:240–249. doi:10.1016/j.tplants.2013.11.007 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Griffith JS (1968) Mathematics of cellular control processes I. Negative feedback to one gene. J Theor Biol 20:202–208. doi:10.1016/0022-5193(68)90189-6 CrossRefPubMedGoogle Scholar
  18. 18.
    Rapp P (1976) Analysis of biochemical phase shift oscillators by a harmonic balancing technique. J Math Biol 3:203–224CrossRefPubMedGoogle Scholar
  19. 19.
    Vanselow K, Vanselow JT, Westermark PO, Reischl S, Maier B, Korte T, Herrmann A, Herzel H, Schlosser A, Kramer A (2006) Differential effects of PER2 phosphorylation: molecular basis for the human familial advanced sleep phase syndrome (FASPS). Genes Dev 20:2660–2672. doi:10.1101/gad.397006 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Reischl S, Vanselow K, Westermark PO, Thierfelder N, Maier B, Herzel H, Kramer A (2007) β-TrCP1-mediated degradation of PERIOD2 is essential for circadian dynamics. J Biol Rhythms 22:375–386. doi:10.1177/0748730407303926 CrossRefPubMedGoogle Scholar
  21. 21.
    Westermark PO, Welsh DK, Okamura H, Herzel H (2009) Quantification of circadian rhythms in single cells. PLoS Comput Biol 5:e1000580. doi:10.1371/journal.pcbi.1000580 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Forger DB (2011) Signal processing in cellular clocks. Proc Natl Acad Sci 108:4281–4285. doi:10.1073/pnas.1004720108 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Relógio A, Westermark PO, Wallach T, Schellenberg K, Kramer A, Herzel H (2011) Tuning the mammalian circadian clock: robust synergy of two loops. PLoS Comput Biol 7:e1002309. doi:10.1371/journal.pcbi.1002309 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    St. John PC, Hirota T, Kay SA, Doyle FJ (2014) Spatiotemporal separation of PER and CRY posttranslational regulation in the mammalian circadian clock. Proc Natl Acad Sci 111:2040–2045. doi:10.1073/pnas.1323618111 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Allada R, Chung BY (2010) Circadian organization of behavior and physiology in Drosophila. Annu Rev Physiol 72:605–624. doi:10.1146/annurev-physiol-021909-135815 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Baker CL, Loros JJ, Dunlap JC (2012) The circadian clock of Neurospora crassa. FEMS Microbiol Rev 36:95–110. doi:10.1111/j.1574-6976.2011.00288.x CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Lee K, Loros JJ, Dunlap JC (2000) Interconnected feedback loops in the Neurospora circadian system. Science 289:107–110CrossRefPubMedGoogle Scholar
  28. 28.
    Young MW, Kay SA (2001) Time zones: a comparative genetics of circadian clocks. Nat Rev Genet 2:702–715. doi:10.1038/35088576 CrossRefPubMedGoogle Scholar
  29. 29.
    Pokhilko A, Fernández AP, Edwards KD, Southern MM, Halliday KJ, Millar AJ (2012) The clock gene circuit in Arabidopsis includes a repressilator with additional feedback loops. Mol Syst Biol 8:574. doi:10.1038/msb.2012.6 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    O’Neill JS, Reddy AB (2011) Circadian clocks in human red blood cells. Nature 469:498–503. doi:10.1038/nature09702 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Hankins MW, Peirson SN, Foster RG (2008) Melanopsin: an exciting photopigment. Trends Neurosci 31:27–36. doi:10.1016/j.tins.2007.11.002 CrossRefPubMedGoogle Scholar
  32. 32.
    Golombek DA, Rosenstein RE (2010) Physiology of circadian entrainment. Physiol Rev 90:1063–1102. doi:10.1152/physrev.00009.2009 CrossRefPubMedGoogle Scholar
  33. 33.
    Dibner C, Schibler U, Albrecht U (2010) The mammalian circadian timing system: organization and coordination of central and peripheral clocks. Annu Rev Physiol 72:517–549. doi:10.1146/annurev-physiol-021909-135821 CrossRefPubMedGoogle Scholar
  34. 34.
    Lincoln G, Andersson H, Loudon A (2003) Clock genes in calendar cells as the basis of annual timekeeping in mammals—a unifying hypothesis. J Endocrinol 179:1–13. doi:10.1677/joe.0.1790001 CrossRefPubMedGoogle Scholar
  35. 35.
    Pévet P, Agez L, Bothorel B, Saboureau M, Gauer F, Laurent V, Masson-Pévet M (2006) Melatonin in the multi-oscillatory mammalian circadian world. Chronobiol Int 23:39–51. doi:10.1080/07420520500482074 CrossRefPubMedGoogle Scholar
  36. 36.
    Dickmeis T (2009) Glucocorticoids and the circadian clock. J Endocrinol 200:3–22. doi:10.1677/JOE-08-0415 CrossRefPubMedGoogle Scholar
  37. 37.
    Menaker M, Murphy ZC, Sellix MT (2013) Central control of peripheral circadian oscillators. Curr Opin Neurobiol 23:741–746. doi:10.1016/j.conb.2013.03.003 CrossRefPubMedGoogle Scholar
  38. 38.
    Tosches MA, Bucher D, Vopalensky P, Arendt D (2014) Melatonin signaling controls circadian swimming behavior in marine zooplankton. Cell 159:46–57. doi:10.1016/j.cell.2014.07.042 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Mistlberger RE (2011) Neurobiology of food anticipatory circadian rhythms. Physiol Behav 104:535–545. doi:10.1016/j.physbeh.2011.04.015 CrossRefPubMedGoogle Scholar
  40. 40.
    Zhang R, Lahens NF, Ballance HI, Hughes ME, Hogenesch JB (2014) A circadian gene expression atlas in mammals: implications for biology and medicine. Proc Natl Acad Sci 111:16219–16224. doi:10.1073/pnas.1408886111 CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Hong CI, Zámborszky J, Baek M, Labiscsak L, Ju K, Lee H, Larrondo LF, Goity A, Chong HS, Belden WJ, Csikász-Nagy A (2014) Circadian rhythms synchronize mitosis in Neurospora crassa. Proc Natl Acad Sci 111:1397–1402. doi:10.1073/pnas.1319399111 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Feillet C, Krusche P, Tamanini F, Janssens RC, Downey MJ, Martin P, Teboul M, Saito S, Lévi FA, Bretschneider T, van der Horst GTJ, Delaunay F, Rand DA (2014) Phase locking and multiple oscillating attractors for the coupled mammalian clock and cell cycle. Proc Natl Acad Sci 111:9828–9833. doi:10.1073/pnas.1320474111 CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Bieler J, Cannavo R, Gustafson K, Gobet C, Gatfield D, Naef F (2014) Robust synchronization of coupled circadian and cell cycle oscillators in single mammalian cells. Mol Syst Biol 10:739. doi:10.15252/msb.20145218 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Kang T-H, Lindsey-Boltz LA, Reardon JT, Sancar A (2010) Circadian control of XPA and excision repair of cisplatin-DNA damage by cryptochrome and HERC2 ubiquitin ligase. Proc Natl Acad Sci 107:4890–4895. doi:10.1073/pnas.0915085107 CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Janich P, Pascual G, Merlos-Suárez A, Batlle E, Ripperger J, Albrecht U, Cheng H-YM, Obrietan K, Di Croce L, Benitah SA (2011) The circadian molecular clock creates epidermal stem cell heterogeneity. Nature 480:209–214. doi:10.1038/nature10649 CrossRefPubMedGoogle Scholar
  46. 46.
    Ma D, Panda S, Lin JD (2011) Temporal orchestration of circadian autophagy rhythm by C/EBPβ. EMBO J 30:4642–4651. doi:10.1038/emboj.2011.322 CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Keller M, Mazuch J, Abraham U, Eom GD, Herzog ED, Volk HD, Kramer A, Maier B (2009) A circadian clock in macrophages controls inflammatory immune responses. Proc Natl Acad Sci 106:21407–21412. doi:10.1073/pnas.0906361106 CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Bass J, Takahashi JS (2010) Circadian integration of metabolism and energetics. Science 330:1349–1354. doi:10.1126/science.1195027 CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Rey G, Reddy AB (2013) Connecting cellular metabolism to circadian clocks. Trends Cell Biol 23:234–241. doi:10.1016/j.tcb.2013.01.003 CrossRefPubMedGoogle Scholar
  50. 50.
    Moore-Ede MC (1986) Physiology of the circadian timing system: predictive versus reactive homeostasis. Am J Physiol - Regul Integr Comp Physiol 250:R737–R752Google Scholar
  51. 51.
    Turek FW, Joshu C, Kohsaka A, Lin E, Ivanova G, McDearmon E, Laposky A, Losee-Olson S, Easton A, Jensen DR, Eckel RH, Takahashi JS, Bass J (2005) Obesity and metabolic syndrome in circadian clock mutant mice. Science 308:1043–1045. doi:10.1126/science.1108750 CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Davis S, Mirick DK (2006) Circadian disruption, shift work and the risk of cancer: a summary of the evidence and studies in Seattle. Cancer Causes Control 17:539–545. doi:10.1007/s10552-005-9010-9 CrossRefPubMedGoogle Scholar
  53. 53.
    Brown SA, Kunz D, Dumas A, Westermark PO, Vanselow K, Tilmann-Wahnschaffe A, Herzel H, Kramer A (2008) Molecular insights into human daily behavior. Proc Natl Acad Sci 105:1602–1607CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Anea CB, Zhang M, Stepp DW, Simkins GB, Reed G, Fulton DJ, Rudic RD (2009) Vascular disease in mice with a dysfunctional circadian clock. Circulation 119:1510–1517. doi:10.1161/CIRCULATIONAHA.108.827477 CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Gibson EM, Williams WP III, Kriegsfeld LJ (2009) Aging in the circadian system: considerations for health, disease prevention and longevity. Exp Gerontol 44:51–56. doi:10.1016/j.exger.2008.05.007 CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Marcheva B, Ramsey KM, Buhr ED, Kobayashi Y, Su H, Ko CH, Ivanova G, Omura C, Mo S, Vitaterna MH, Lopez JP, Philipson LH, Bradfield CA, Crosby SD, JeBailey L, Wang X, Takahashi JS, Bass J (2010) Disruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes. Nature 466:627–631. doi:10.1038/nature09253 CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Bonny O, Vinciguerra M, Gumz ML, Mazzoccoli G (2013) Molecular bases of circadian rhythmicity in renal physiology and pathology. Nephrol Dial Transplant 28:2421–2431. doi:10.1093/ndt/gft319 CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Scheving LE (1959) Mitotic activity in the human epidermis. Anat Rec 135:7–19. doi:10.1002/ar.1091350103 CrossRefPubMedGoogle Scholar
  59. 59.
    Andrews RV, Folk GE Jr (1964) Circadian metabolic patterns in cultured hamster adrenal glands. Comp Biochem Physiol 11:393–409CrossRefPubMedGoogle Scholar
  60. 60.
    Rapoport MI, Feigin RD, Bruton J, Beisel WR (1966) Circadian rhythm for tryptophan pyrrolase activity and its circulating substrate. Science 153:1642–1644. doi:10.1126/science.153.3744.1642 CrossRefPubMedGoogle Scholar
  61. 61.
    Civen M, Ulrich R, Trimmer BM, Brown CB (1967) Circadian rhythms of liver enzymes and their relationship to enzyme induction. Science 157:1563–1564CrossRefPubMedGoogle Scholar
  62. 62.
    Mitropoulos KA, Balasubramaniam S, Gibbons GF, Reeves BEA (1972) Diurnal variation in the activity of cholesterol 7α-hydroxylase in the livers of fed and fasted rats. FEBS Lett 27:203–206. doi:10.1016/0014-5793(72)80620-3 CrossRefPubMedGoogle Scholar
  63. 63.
    Feuers RJ, Delongchamp RR, Scheving LE, Casciano DA, Tsai TH, Pauly JE (1986) The effects of various lighting schedules upon the circadian rhythms of 23 liver or brain enzymes of C57BL/6 J mice. Chronobiol Int 3:221–235CrossRefPubMedGoogle Scholar
  64. 64.
    Clarke CF, Fogelman AM, Edwards PA (1984) Diurnal rhythm of rat liver mRNAs encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase. Correlation of functional and total mRNA levels with enzyme activity and protein. J Biol Chem 259:10439–10447PubMedGoogle Scholar
  65. 65.
    Wuarin J, Schibler U (1990) Expression of the liver-enriched transcriptional activator protein DBP follows a stringent circadian rhythm. Cell 63:1257–1266. doi:10.1016/0092-8674(90)90421-A CrossRefPubMedGoogle Scholar
  66. 66.
    Hogenesch JB, Gu Y-Z, Jain S, Bradfield CA (1998) The basic-helix–loop–helix-PAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors. Proc Natl Acad Sci 95:5474–5479CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Jin X, Shearman LP, Weaver DR, Zylka MJ, De Vries GJ, Reppert SM (1999) A molecular mechanism regulating rhythmic output from the suprachiasmatic circadian clock. Cell 96:57–68. doi:10.1016/S0092-8674(00)80959-9 CrossRefPubMedGoogle Scholar
  68. 68.
    Lavery DJ, Schibler U (1993) Circadian transcription of the cholesterol 7 alpha hydroxylase gene may involve the liver-enriched bZIP protein DBP. Genes Dev 7:1871–1884. doi:10.1101/gad.7.10.1871 CrossRefPubMedGoogle Scholar
  69. 69.
    Harmer SL, Hogenesch JB, Straume M, Chang H-S, Han B, Zhu T, Wang X, Kreps JA, Kay SA (2000) Orchestrated transcription of key pathways in Arabidopsis by the circadian clock. Science 290:2110–2113. doi:10.1126/science.290.5499.2110 CrossRefPubMedGoogle Scholar
  70. 70.
    Claridge-Chang A, Wijnen H, Naef F, Boothroyd C, Rajewsky N, Young MW (2001) Circadian regulation of gene expression systems in the Drosophila head. Neuron 32:657–671. doi:10.1016/S0896-6273(01)00515-3 CrossRefPubMedGoogle Scholar
  71. 71.
    Grundschober C, Delaunay F, Pühlhofer A, Triqueneaux G, Laudet V, Bartfai T, Nef P (2001) Circadian regulation of diverse gene products revealed by mRNA expression profiling of synchronized fibroblasts. J Biol Chem 276:46751–46758. doi:10.1074/jbc.M107499200 CrossRefPubMedGoogle Scholar
  72. 72.
    Panda S, Antoch MP, Miller BH, Su AI, Schook AB, Straume M, Schultz PG, Kay SA, Takahashi JS, Hogenesch JB (2002) Coordinated transcription of key pathways in the mouse by the circadian clock. Cell 109:307–320. doi:10.1016/S0092-8674(02)00722-5 CrossRefPubMedGoogle Scholar
  73. 73.
    Storch K-F, Lipan O, Leykin I, Viswanathan N, Davis FC, Wong WH, Weitz CJ (2002) Extensive and divergent circadian gene expression in liver and heart. Nature 417:78–83. doi:10.1038/nature744 CrossRefPubMedGoogle Scholar
  74. 74.
    Ueda HR, Chen W, Adachi A, Wakamatsu H, Hayashi S, Takasugi T, Nagano M, Nakahama K, Suzuki Y, Sugano S, Iino M, Shigeyoshi Y, Hashimoto S (2002) A transcription factor response element for gene expression during circadian night. Nature 418:534–539. doi:10.1038/nature00906 CrossRefPubMedGoogle Scholar
  75. 75.
    Oster H, Damerow S, Hut RA, Eichele G (2006) Transcriptional profiling in the adrenal gland reveals circadian regulation of hormone biosynthesis genes and nucleosome assembly genes. J Biol Rhythms 21:350–361. doi:10.1177/0748730406293053 CrossRefPubMedGoogle Scholar
  76. 76.
    Oster H, Damerow S, Kiessling S, Jakubcakova V, Abraham D, Tian J, Hoffmann MW, Eichele G (2006) The circadian rhythm of glucocorticoids is regulated by a gating mechanism residing in the adrenal cortical clock. Cell Metab 4:163–173. doi:10.1016/j.cmet.2006.07.002 CrossRefPubMedGoogle Scholar
  77. 77.
    Zvonic S, Ptitsyn AA, Conrad SA, Scott LK, Floyd ZE, Kilroy G, Wu X, Goh BC, Mynatt RL, Gimble JM (2006) Characterization of peripheral circadian clocks in adipose tissues. Diabetes 55:962–970. doi:10.2337/diabetes.55.04.06.db05-0873 CrossRefPubMedGoogle Scholar
  78. 78.
    Zvonic S, Ptitsyn AA, Kilroy G, Wu X, Conrad SA, Scott LK, Guilak F, Pelled G, Gazit D, Gimble JM (2006) Circadian oscillation of gene expression in murine calvarial bone. J Bone Miner Res 22:357–365. doi:10.1359/jbmr.061114 CrossRefGoogle Scholar
  79. 79.
    Hughes M, Deharo L, Pulivarthy SR, Gu J, Hayes K, Panda S, Hogenesch JB (2007) High-resolution time course analysis of gene expression from pituitary. Cold Spring Harb Symp Quant Biol 72:381–386. doi:10.1101/sqb.2007.72.011 CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    McCarthy JJ, Andrews JL, McDearmon EL, Campbell KS, Barber BK, Miller BH, Walker JR, Hogenesch JB, Takahashi JS, Esser KA (2007) Identification of the circadian transcriptome in adult mouse skeletal muscle. Physiol Genomics 31:86–95. doi:10.1152/physiolgenomics.00066.2007 CrossRefPubMedGoogle Scholar
  81. 81.
    Storch K-F, Paz C, Signorovitch J, Raviola E, Pawlyk B, Li T, Weitz CJ (2007) Intrinsic circadian clock of the mammalian retina: importance for retinal processing of visual information. Cell 130:730–741. doi:10.1016/j.cell.2007.06.045 CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Hoogerwerf WA, Sinha M, Conesa A, Luxon BA, Shahinian VB, Cornélissen G, Halberg F, Bostwick J, Timm J, Cassone VM (2008) Transcriptional profiling of mRNA expression in the mouse distal colon. Gastroenterology 135:2019–2029. doi:10.1053/j.gastro.2008.08.048 CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Zuber AM, Centeno G, Pradervand S, Nikolaeva S, Maquelin L, Cardinaux L, Bonny O, Firsov D (2009) Molecular clock is involved in predictive circadian adjustment of renal function. Proc Natl Acad Sci 106:16523–16528. doi:10.1073/pnas.0904890106 CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Hughes ME, DiTacchio L, Hayes KR, Vollmers C, Pulivarthy S, Baggs JE, Panda S, Hogenesch JB (2009) Harmonics of circadian gene transcription in mammals. PLoS Genet 5:e1000442. doi:10.1371/journal.pgen.1000442 CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Atwood A, DeConde R, Wang SS, Mockler TC, Sabir JSM, Ideker T, Kay SA (2011) Cell-autonomous circadian clock of hepatocytes drives rhythms in transcription and polyamine synthesis. Proc Natl Acad Sci 108:18560–18565. doi:10.1073/pnas.1115753108 CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Cretenet G, Le Clech M, Gachon F (2010) Circadian clock-coordinated 12 hr period rhythmic activation of the IRE1 alpha pathway controls lipid metabolism in mouse liver. Cell Metab 11:47–57. doi:10.1016/j.cmet.2009.11.002 CrossRefPubMedGoogle Scholar
  87. 87.
    Kornmann B, Schaad O, Bujard H, Takahashi JS, Schibler U (2007) System-driven and oscillator-dependent circadian transcription in mice with a conditionally active liver clock. PLoS Biol 5:e34. doi:10.1371/journal.pbio.0050034 CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Vollmers C, Gill S, DiTacchio L, Pulivarthy SR, Le HD, Panda S (2009) Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression. Proc Natl Acad Sci 106:21453–21458. doi:10.1073/pnas.0909591106 CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Eckel-Mahan KL, Patel VR, de Mateo S, Orozco-Solis R, Ceglia NJ, Sahar S, Dilag-Penilla SA, Dyar KA, Baldi P, Sassone-Corsi P (2013) Reprogramming of the circadian clock by nutritional challenge. Cell 155:1464–1478. doi:10.1016/j.cell.2013.11.034 CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Masri S, Rigor P, Cervantes M, Ceglia N, Sebastian C, Xiao C, Roqueta-Rivera M, Deng C, Osborne TF, Mostoslavsky R, Baldi P, Sassone-Corsi P (2014) Partitioning circadian transcription by SIRT6 leads to segregated control of cellular metabolism. Cell 158:659–672. doi:10.1016/j.cell.2014.06.050 CrossRefPubMedGoogle Scholar
  91. 91.
    Hatori M, Hirota T, Iitsuka M, Kurabayashi N, Haraguchi S, Kokame K, Sato R, Nakai A, Miyata T, Tsutsui K, Fukada Y (2011) Light-dependent and circadian clock-regulated activation of sterol regulatory element-binding protein, X-box-binding protein 1, and heat shock factor pathways. Proc Natl Acad Sci 108:4864–4869. doi:10.1073/pnas.1015959108 CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Fustin J-M, Doi M, Yamada H, Komatsu R, Shimba S, Okamura H (2012) Rhythmic nucleotide synthesis in the liver: temporal segregation of metabolites. Cell Rep 1:341–349. doi:10.1016/j.celrep.2012.03.001 CrossRefPubMedGoogle Scholar
  93. 93.
    Eckel-Mahan KL, Patel VR, Mohney RP, Vignola KS, Baldi P, Sassone-Corsi P (2012) Coordination of the transcriptome and metabolome by the circadian clock. Proc Natl Acad Sci 109:5541–5546. doi:10.1073/pnas.1118726109 CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Dyar KA, Ciciliot S, Wright LE, Biensø RS, Tagliazucchi GM, Patel VR, Forcato M, Paz MIP, Gudiksen A, Solagna F, Albiero M, Moretti I, Eckel-Mahan KL, Baldi P, Sassone-Corsi P, Rizzuto R, Bicciato S, Pilegaard H, Blaauw B, Schiaffino S (2014) Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic muscle clock. Mol Metab 3:29–41. doi:10.1016/j.molmet.2013.10.005 CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Patel SA, Velingkaar NS, Kondratov RV (2014) Transcriptional control of antioxidant defense by the circadian clock. Antioxid Redox Signal 20:2997–3006. doi:10.1089/ars.2013.5671 CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Klein DC, Coon SL, Roseboom PH, Weller JL, Bernard M, Gastel JA, Zatz M, Iuvone PM, Rodriguez IR, Bégay V, Falcón J, Cahill GM, Cassone VM, Baler R (1997) The melatonin rhythm-generating enzyme: molecular regulation of serotonin N-acetyltransferase in the pineal gland. Recent Prog Horm Res 52:307–357 (discussion 357–358) PubMedGoogle Scholar
  97. 97.
    Cornish-Bowden A (2012) Fundamentals of enzyme kinetics, 4th edn. Wiley-Blackwell, WeinheimGoogle Scholar
  98. 98.
    Oliver S (2002) Metabolism: demand management in cells. Nature 418:33–34. doi:10.1038/418033a CrossRefPubMedGoogle Scholar
  99. 99.
    Halberg F, Tong YL, Johnson EA (1967) Circadian system phase— an aspect of temporal morphology; procedures and illustrative examples. In: von Mayersbach H (ed) Cell. Asp. Biorhythms, Springer, pp 20–48Google Scholar
  100. 100.
    Wijnen H, Naef F, Young MW (2005) Molecular and statistical tools for circadian transcript profiling. In: Methods Enzymol. Academic Press, pp 341–365Google Scholar
  101. 101.
    Hughes ME, Hogenesch JB, Kornacker K (2010) JTK_CYCLE: an efficient nonparametric algorithm for detecting rhythmic components in genome-scale data sets. J Biol Rhythms 25:372–380. doi:10.1177/0748730410379711 CrossRefPubMedPubMedCentralGoogle Scholar
  102. 102.
    Thaben PF, Westermark PO (2014) Detecting rhythms in time series with RAIN. J Biol Rhythms 29:391–400. doi:10.1177/0748730414553029 CrossRefPubMedPubMedCentralGoogle Scholar
  103. 103.
    Benjamini Y, Hochberg Y (2000) On the adaptive control of the false discovery rate in multiple testing with independent statistics. J Educ Behav Stat 25:60–83. doi:10.3102/10769986025001060 CrossRefGoogle Scholar
  104. 104.
    Storey JD, Tibshirani R (2003) Statistical significance for genomewide studies. Proc Natl Acad Sci 100:9440–9445. doi:10.1073/pnas.1530509100 CrossRefPubMedPubMedCentralGoogle Scholar
  105. 105.
    Strimmer K (2008) A unified approach to false discovery rate estimation. BMC Bioinformatics 9:303. doi:10.1186/1471-2105-9-303 CrossRefPubMedPubMedCentralGoogle Scholar
  106. 106.
    Ma D, Li S, Molusky MM, Lin JD (2012) Circadian autophagy rhythm: a link between clock and metabolism? Trends Endocrinol Metab 23:319–325. doi:10.1016/j.tem.2012.03.004 CrossRefPubMedPubMedCentralGoogle Scholar
  107. 107.
    Goentoro L, Shoval O, Kirschner MW, Alon U (2009) The incoherent feedforward loop can provide fold-change detection in gene regulation. Mol Cell 36:894–899. doi:10.1016/j.molcel.2009.11.018 CrossRefPubMedPubMedCentralGoogle Scholar
  108. 108.
    Alegria FC (2009) Bias of amplitude estimation using three-parameter sine fitting in the presence of additive noise. Measurement 42:748–756. doi:10.1016/j.measurement.2008.12.006 CrossRefGoogle Scholar
  109. 109.
    Nuzzo R (2014) Scientific method: statistical errors. Nature 506:150–152. doi:10.1038/506150a CrossRefPubMedGoogle Scholar
  110. 110.
    Murdoch DJ, Tsai Y-L, Adcock J (2008) P values are random variables. Am Stat 62:242–245CrossRefGoogle Scholar
  111. 111.
    Rey G, Cesbron F, Rougemont J, Reinke H, Brunner M, Naef F (2011) Genome-wide and phase-specific DNA-binding rhythms of BMAL1 control circadian output functions in mouse liver. PLoS Biol 9:e1000595. doi:10.1371/journal.pbio.1000595 CrossRefPubMedPubMedCentralGoogle Scholar
  112. 112.
    Stratmann M, Suter DM, Molina N, Naef F, Schibler U (2012) Circadian Dbp transcription relies on highly dynamic BMAL1-CLOCK interaction with E boxes and requires the proteasome. Mol Cell 48:277–287. doi:10.1016/j.molcel.2012.08.012 CrossRefPubMedGoogle Scholar
  113. 113.
    Lee C, Etchegaray J-P, Cagampang FRA, Loudon ASI, Reppert SM (2001) Posttranslational mechanisms regulate the mammalian circadian clock. Cell 107:855–867. doi:10.1016/S0092-8674(01)00610-9 CrossRefPubMedGoogle Scholar
  114. 114.
    Ripperger JA, Schibler U (2006) Rhythmic CLOCK-BMAL1 binding to multiple E-box motifs drives circadian Dbp transcription and chromatin transitions. Nat Genet 38:369–374. doi:10.1038/ng1738 CrossRefPubMedGoogle Scholar
  115. 115.
    Fustin JM, O’Neill JS, Hastings MH, Hazlerigg DG, Dardente H (2009) Cry1 circadian phase in vitro: wrapped up with an E-box. J Biol Rhythms 24:16–24. doi:10.1177/0748730408329267 CrossRefPubMedGoogle Scholar
  116. 116.
    Mitsui S, Yamaguchi S, Matsuo T, Ishida Y, Okamura H (2001) Antagonistic role of E4BP4 and PAR proteins in the circadian oscillatory mechanism. Genes Dev 15:995–1006. doi:10.1101/gad.873501 CrossRefPubMedPubMedCentralGoogle Scholar
  117. 117.
    Gachon F, Olela FF, Schaad O, Descombes P, Schibler U (2006) The circadian PAR-domain basic leucine zipper transcription factors DBP, TEF, and HLF modulate basal and inducible xenobiotic detoxification. Cell Metab 4:25–36. doi:10.1016/j.cmet.2006.04.015 CrossRefPubMedGoogle Scholar
  118. 118.
    Fang B, Everett LJ, Jager J, Briggs E, Armour SM, Feng D, Roy A, Gerhart-Hines Z, Sun Z, Lazar MA (2014) Circadian enhancers coordinate multiple phases of rhythmic gene transcription in vivo. Cell 159:1140–1152. doi:10.1016/j.cell.2014.10.022 CrossRefPubMedPubMedCentralGoogle Scholar
  119. 119.
    Preitner N, Damiola F, Luis-Lopez-Molina Zakany J, Duboule D, Albrecht U, Schibler U (2002) The orphan nuclear receptor Rev-erbα controls circadian transcription within the positive limb of the mammalian circadian oscillator. Cell 110:251–260. doi:10.1016/S0092-8674(02)00825-5 CrossRefPubMedGoogle Scholar
  120. 120.
    Ukai-Tadenuma M, Yamada RG, Xu H, Ripperger JA, Liu AC, Ueda HR (2011) Delay in feedback repression by cryptochrome 1 is required for circadian clock function. Cell 144:268–281. doi:10.1016/j.cell.2010.12.019 CrossRefPubMedGoogle Scholar
  121. 121.
    Ueda HR, Hayashi S, Chen W, Sano M, Machida M, Shigeyoshi Y, Iino M, Hashimoto S (2005) System-level identification of transcriptional circuits underlying mammalian circadian clocks. Nat Genet 37:187–192. doi:10.1038/ng1504 CrossRefPubMedGoogle Scholar
  122. 122.
    Yin L, Wu N, Curtin JC, Qatanani M, Szwergold NR, Reid RA, Waitt GM, Parks DJ, Pearce KH, Wisely GB, Lazar MA (2007) Rev-erbα, a heme sensor that coordinates metabolic and circadian pathways. Science 318:1786–1789. doi:10.1126/science.1150179 CrossRefPubMedGoogle Scholar
  123. 123.
    Cho H, Zhao X, Hatori M, Yu RT, Barish GD, Lam MT, Chong L-W, DiTacchio L, Atkins AR, Glass CK, Liddle C, Auwerx J, Downes M, Panda S, Evans RM (2012) Regulation of circadian behaviour and metabolism by REV-ERB-α and REV-ERB-β. Nature 485:123–127. doi:10.1038/nature11048 CrossRefPubMedPubMedCentralGoogle Scholar
  124. 124.
    Bugge A, Feng D, Everett LJ, Briggs ER, Mullican SE, Wang F, Jager J, Lazar MA (2012) Rev-erbα and Rev-erbβ coordinately protect the circadian clock and normal metabolic function. Genes Dev 26:657–667. doi:10.1101/gad.186858.112 CrossRefPubMedPubMedCentralGoogle Scholar
  125. 125.
    Bunger MK, Wilsbacher LD, Moran SM, Clendenin C, Radcliffe LA, Hogenesch JB, Simon MC, Takahashi JS, Bradfield CA (2000) Mop3 is an essential component of the master circadian pacemaker in mammals. Cell 103:1009–1017. doi:10.1016/S0092-8674(00)00205-1 CrossRefPubMedPubMedCentralGoogle Scholar
  126. 126.
    Gekakis N, Staknis D, Nguyen HB, Davis FC, Wilsbacher LD, King DP, Takahashi JS, Weitz CJ (1998) Role of the CLOCK protein in the mammalian circadian mechanism. Science 280:1564–1569. doi:10.1126/science.280.5369.1564 CrossRefPubMedGoogle Scholar
  127. 127.
    Hida A, Koike N, Hirose M, Hattori M, Sakaki Y, Tei H (2000) The human and mouse Period1 genes: five well-conserved E-boxes additively contribute to the enhancement of mPer1 transcription. Genomics 65:224–233. doi:10.1006/geno.2000.6166 CrossRefPubMedGoogle Scholar
  128. 128.
    Yoo S-H, Ko CH, Lowrey PL, Buhr ED, Song E, Chang S, Yoo OJ, Yamazaki S, Lee C, Takahashi JS (2005) A noncanonical E-box enhancer drives mouse Period2 circadian oscillations in vivo. Proc Natl Acad Sci 102:2608–2613. doi:10.1073/pnas.0409763102 CrossRefPubMedPubMedCentralGoogle Scholar
  129. 129.
    Akashi M, Ichise T, Mamine T, Takumi T (2006) Molecular mechanism of cell-autonomous circadian gene expression of Period2, a crucial regulator of the mammalian circadian clock. Mol Biol Cell 17:555–565. doi:10.1091/mbc.E05-05-0396 CrossRefPubMedPubMedCentralGoogle Scholar
  130. 130.
    Ripperger JA (2006) Mapping of binding regions for the circadian regulators BMAL1 and CLOCK within the mouse Rev-erbα gene. Chronobiol Int 23:135–142. doi:10.1080/07420520500464411 CrossRefPubMedGoogle Scholar
  131. 131.
    Ripperger JA, Shearman LP, Reppert SM, Schibler U (2000) CLOCK, an essential pacemaker component, controls expression of the circadian transcription factor DBP. Genes Dev 14:679–689. doi:10.1101/gad.14.6.679 PubMedPubMedCentralGoogle Scholar
  132. 132.
    Guillaumond F, Dardente H, Giguere V, Cermakian N (2005) Differential control of Bmal1 circadian transcription by REV-ERB and ROR nuclear receptors. J Biol Rhythms 20:391–403. doi:10.1177/0748730405277232 CrossRefPubMedGoogle Scholar
  133. 133.
    Kowalska E, Ripperger JA, Muheim C, Maier B, Kurihara Y, Fox AH, Kramer A, Brown SA (2012) Distinct roles of DBHS family members in the circadian transcriptional feedback loop. Mol Cell Biol 32:4585–4594. doi:10.1128/MCB.00334-12 CrossRefPubMedPubMedCentralGoogle Scholar
  134. 134.
    Lande-Diner L, Boyault C, Kim JY, Weitz CJ (2013) A positive feedback loop links circadian clock factor CLOCK-BMAL1 to the basic transcriptional machinery. Proc Natl Acad Sci 110:16021–16026. doi:10.1073/pnas.1305980110 CrossRefPubMedPubMedCentralGoogle Scholar
  135. 135.
    Rosenfeld MG, Lunyak VV, Glass CK (2006) Sensors and signals: a coactivator/corepressor/epigenetic code for integrating signal-dependent programs of transcriptional response. Genes Dev 20:1405–1428. doi:10.1101/gad.1424806 CrossRefPubMedGoogle Scholar
  136. 136.
    Etchegaray J-P, Lee C, Wade PA, Reppert SM (2003) Rhythmic histone acetylation underlies transcription in the mammalian circadian clock. Nature 421:177–182. doi:10.1038/nature01314 CrossRefPubMedGoogle Scholar
  137. 137.
    Aguilar-Arnal L, Hakim O, Patel VR, Baldi P, Hager GL, Sassone-Corsi P (2013) Cycles in spatial and temporal chromosomal organization driven by the circadian clock. Nat Struct Mol Biol 20:1206–1213. doi:10.1038/nsmb.2667 CrossRefPubMedGoogle Scholar
  138. 138.
    Yin L, Lazar MA (2005) The orphan nuclear receptor Rev-erbα recruits the N-CoR/histone deacetylase 3 corepressor to regulate the circadian Bmal1 gene. Mol Endocrinol 19:1452–1459. doi:10.1210/me.2005-0057 CrossRefPubMedGoogle Scholar
  139. 139.
    Alenghat T, Meyers K, Mullican SE, Leitner K, Adeniji-Adele A, Avila J, Bucan M, Ahima RS, Kaestner KH, Lazar MA (2008) Nuclear receptor corepressor and histone deacetylase 3 govern circadian metabolic physiology. Nature 456:997–1000. doi:10.1038/nature07541 CrossRefPubMedPubMedCentralGoogle Scholar
  140. 140.
    Feng D, Liu T, Sun Z, Bugge A, Mullican S, Alenghat T, Liu X-S, Lazar M (2011) A circadian rhythm orchestrated by histone deacetylase 3 controls hepatic lipid metabolism. Science 331:1315–1319. doi:10.1126/science.1198125 CrossRefPubMedPubMedCentralGoogle Scholar
  141. 141.
    Liu C, Li S, Liu T, Borjigin J, Lin JD (2007) Transcriptional coactivator PGC-1α integrates the mammalian clock and energy metabolism. Nature 447:477–481. doi:10.1038/nature05767 CrossRefPubMedGoogle Scholar
  142. 142.
    Schmutz I, Ripperger JA, Baeriswyl-Aebischer S, Albrecht U (2010) The mammalian clock component PERIOD2 coordinates circadian output by interaction with nuclear receptors. Genes Dev 24:345–357. doi:10.1101/gad.564110 CrossRefPubMedPubMedCentralGoogle Scholar
  143. 143.
    Nakahata Y, Kaluzova M, Grimaldi B, Sahar S, Hirayama J, Chen D, Guarente LP, Sassone-Corsi P (2008) The NAD + -dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control. Cell 134:329–340. doi:10.1016/j.cell.2008.07.002 CrossRefPubMedPubMedCentralGoogle Scholar
  144. 144.
    Katada S, Sassone-Corsi P (2010) The histone methyltransferase MLL1 permits the oscillation of circadian gene expression. Nat Struct Mol Biol 17:1414–1421. doi:10.1038/nsmb.1961 CrossRefPubMedGoogle Scholar
  145. 145.
    DiTacchio L, Le HD, Vollmers C, Hatori M, Witcher M, Secombe J, Panda S (2011) Histone lysine demethylase JARID1a activates CLOCK-BMAL1 and influences the circadian clock. Science 333:1881–1885. doi:10.1126/science.1206022 CrossRefPubMedPubMedCentralGoogle Scholar
  146. 146.
    Raduwan H, Isola AL, Belden WJ (2013) Methylation of histone H3 on lysine 4 by the lysine methyltransferase SET1 protein is needed for normal clock gene expression. J Biol Chem 288:8380–8390. doi:10.1074/jbc.M112.359935 CrossRefPubMedPubMedCentralGoogle Scholar
  147. 147.
    Valekunja UK, Edgar RS, Oklejewicz M, Horst GTJ, O’Neill VD, Tamanini JS, Turner F, Reddy AB (2013) Histone methyltransferase MLL3 contributes to genome-scale circadian transcription. Proc Natl Acad Sci 110:1554–1559. doi:10.1073/pnas.1214168110 CrossRefPubMedPubMedCentralGoogle Scholar
  148. 148.
    Koike N, Yoo S-H, Huang H-C, Kumar V, Lee C, Kim T-K, Takahashi JS (2012) Transcriptional architecture and chromatin landscape of the core circadian clock in mammals. Science 338:349–354. doi:10.1126/science.1226339 CrossRefPubMedPubMedCentralGoogle Scholar
  149. 149.
    Vollmers C, Schmitz RJ, Nathanson J, Yeo G, Ecker JR, Panda S (2012) Circadian oscillations of protein-coding and regulatory RNAs in a highly dynamic mammalian liver epigenome. Cell Metab 16:833–845. doi:10.1016/j.cmet.2012.11.004 CrossRefPubMedPubMedCentralGoogle Scholar
  150. 150.
    Le Martelot G, Canella D, Symul L, Migliavacca E, Gilardi F, Liechti R, Martin O, Harshman K, Delorenzi M, Desvergne B, Herr W, Deplancke B, Schibler U, Rougemont J, Guex N, Hernandez N, Naef F, the CycliX consortium (2012) Genome-wide RNA polymerase II profiles and RNA accumulation reveal kinetics of transcription and associated epigenetic changes during diurnal cycles. PLoS Biol 10:e1001442. doi:10.1371/journal.pbio.1001442 CrossRefPubMedPubMedCentralGoogle Scholar
  151. 151.
    Menet JS, Pescatore S, Rosbash M (2014) CLOCK:bMAL1 is a pioneer-like transcription factor. Genes Dev 28:8–13. doi:10.1101/gad.228536.113 CrossRefPubMedPubMedCentralGoogle Scholar
  152. 152.
    Kumaki Y, Ukai-Tadenuma M, Uno K, Nishio J, Masumoto K, Nagano M, Komori T, Shigeyoshi Y, Hogenesch J, Ueda HR (2008) Analysis and synthesis of high-amplitude Cis-elements in the mammalian circadian clock. Proc Natl Acad Sci 105:14946–14951. doi:10.1073/pnas.0802636105 CrossRefPubMedPubMedCentralGoogle Scholar
  153. 153.
    Ukai-Tadenuma M, Kasukawa T, Ueda HR (2008) Proof-by-synthesis of the transcriptional logic of mammalian circadian clocks. Nat Cell Biol 10:1154–1163. doi:10.1038/ncb1775 CrossRefPubMedGoogle Scholar
  154. 154.
    Westermark PO, Herzel H (2013) Mechanism for 12 hr rhythm generation by the circadian clock. Cell Rep 3:1228–1238. doi:10.1016/j.celrep.2013.03.013 CrossRefPubMedGoogle Scholar
  155. 155.
    Ohno T, Onishi Y, Ishida N (2007) A novel E4BP4 element drives circadian expression of mPeriod2. Nucleic Acids Res 35:648–655. doi:10.1093/nar/gkl868 CrossRefPubMedPubMedCentralGoogle Scholar
  156. 156.
    Yamajuku D, Shibata Y, Kitazawa M, Katakura T, Urata H, Kojima T, Nakata O, Hashimoto S (2010) Identification of functional clock-controlled elements involved in differential timing of Per1 and Per2 transcription. Nucleic Acids Res 38:7964–7973. doi:10.1093/nar/gkq678 CrossRefPubMedPubMedCentralGoogle Scholar
  157. 157.
    Nakashima A, Kawamoto T, Honda KK, Ueshima T, Noshiro M, Iwata T, Fujimoto K, Kubo H, Honma S, Yorioka N, Kohno N, Kato Y (2008) DEC1 modulates the circadian phase of clock gene expression. Mol Cell Biol 28:4080–4092. doi:10.1128/MCB.02168-07 CrossRefPubMedPubMedCentralGoogle Scholar
  158. 158.
    Xu Z, Chen H, Ling J, Yu D, Struffi P, Small S (2014) Impacts of the ubiquitous factor Zelda on Bicoid-dependent DNA binding and transcription in Drosophila. Genes Dev 28:608–621. doi:10.1101/gad.234534.113 CrossRefPubMedPubMedCentralGoogle Scholar
  159. 159.
    Stratmann M, Stadler F, Tamanini F, van der Horst GTJ, Ripperger JA (2010) Flexible phase adjustment of circadian albumin D site-binding protein (Dbp) gene expression by CRYPTOCHROME1. Genes Dev 24:1317–1328. doi:10.1101/gad.578810 CrossRefPubMedPubMedCentralGoogle Scholar
  160. 160.
    Stormo GD (2000) DNA binding sites: representation and discovery. Bioinformatics 16:16–23. doi:10.1093/bioinformatics/16.1.16 CrossRefPubMedGoogle Scholar
  161. 161.
    Wasserman WW, Sandelin A (2004) Applied bioinformatics for the identification of regulatory elements. Nat Rev Genet 5:276–287. doi:10.1038/nrg1315 CrossRefPubMedGoogle Scholar
  162. 162.
    Frith MC, Fu Y, Yu L, Chen J-F, Hansen U, Weng Z (2004) Detection of functional DNA motifs via statistical over-representation. Nucl Acids Res 32:1372–1381. doi:10.1093/nar/gkh299 CrossRefPubMedPubMedCentralGoogle Scholar
  163. 163.
    Pachkov M, Erb I, Molina N, van Nimwegen E (2007) SwissRegulon: a database of genome-wide annotations of regulatory sites. Nucleic Acids Res 35:D127–D131. doi:10.1093/nar/gkl857 CrossRefPubMedPubMedCentralGoogle Scholar
  164. 164.
    Yan J, Wang H, Liu Y, Shao C (2008) Analysis of gene regulatory networks in the mammalian circadian rhythm. PLoS Comput Biol 4:e1000193. doi:10.1371/journal.pcbi.1000193 CrossRefPubMedPubMedCentralGoogle Scholar
  165. 165.
    Bozek K, Relógio A, Kielbasa SM, Heine M, Dame C, Kramer A, Herzel H (2009) Regulation of clock-controlled genes in mammals. PLoS One 4:e4882. doi:10.1371/journal.pone.0004882 CrossRefPubMedPubMedCentralGoogle Scholar
  166. 166.
    Vaquerizas J, Kummerfeld S, Teichmann S, Luscombe N (2009) A census of human transcription factors: function, expression and evolution. Nat Rev Genet 10:252–263. doi:10.1038/nrg2538 CrossRefPubMedGoogle Scholar
  167. 167.
    Reinke H, Saini C, Fleury-Olela F, Dibner C, Benjamin IJ, Schibler U (2008) Differential display of DNA-binding proteins reveals heat-shock factor 1 as a circadian transcription factor. Genes Dev 22:331–345. doi:10.1101/gad.453808 CrossRefPubMedPubMedCentralGoogle Scholar
  168. 168.
    Korenčič A, Košir R, Bordyugov G, Lehmann R, Rozman D, Herzel H (2014) Timing of circadian genes in mammalian tissues. Sci Rep 4:5782. doi:10.1038/srep05782 CrossRefPubMedGoogle Scholar
  169. 169.
    Merika M, Thanos D (2001) Enhanceosomes. Curr Opin Genet Dev 11:205–208. doi:10.1016/S0959-437X(00)00180-5 CrossRefPubMedGoogle Scholar
  170. 170.
    Arnosti DN, Kulkarni MM (2005) Transcriptional enhancers: intelligent enhanceosomes or flexible billboards? J Cell Biochem 94:890–898. doi:10.1002/jcb.20352 CrossRefPubMedGoogle Scholar
  171. 171.
    Lück S, Thurley K, Thaben PF, Westermark PO (2014) Rhythmic degradation explains and unifies circadian transcriptome and proteome data. Cell Rep 9:741–751. doi:10.1016/j.celrep.2014.09.021 CrossRefPubMedGoogle Scholar
  172. 172.
    Wuarin J, Falvey E, Lavery D, Talbot D, Schmidt E, Ossipow V, Fonjallaz P, Schibler U (1992) The role of the transcriptional activator protein DBP in circadian liver gene expression. J Cell Sci Suppl 16:123–127CrossRefPubMedGoogle Scholar
  173. 173.
    Swinburne IA, Miguez DG, Landgraf D, Silver PA (2008) Intron length increases oscillatory periods of gene expression in animal cells. Genes Dev 22:2342–2346. doi:10.1101/gad.1696108 CrossRefPubMedPubMedCentralGoogle Scholar
  174. 174.
    Singh J, Padgett RA (2009) Rates of in situ transcription and splicing in large human genes. Nat Struct Mol Biol 16:1128–1133. doi:10.1038/nsmb.1666 CrossRefPubMedPubMedCentralGoogle Scholar
  175. 175.
    Schwanhausser B, Busse D, Li N, Dittmar G, Schuchhardt J, Wolf J, Chen W, Selbach M (2011) Global quantification of mammalian gene expression control. Nature 473:337–342. doi:10.1038/nature10098 CrossRefPubMedGoogle Scholar
  176. 176.
    Chen WW, Niepel M, Sorger PK (2010) Classic and contemporary approaches to modeling biochemical reactions. Genes Dev 24:1861–1875. doi:10.1101/gad.1945410 CrossRefPubMedPubMedCentralGoogle Scholar
  177. 177.
    Bar-Even A, Noor E, Savir Y, Liebermeister W, Davidi D, Tawfik DS, Milo R (2011) The moderately efficient enzyme: evolutionary and physicochemical trends shaping enzyme parameters. Biochemistry 50:4402–4410. doi:10.1021/bi2002289 CrossRefPubMedGoogle Scholar
  178. 178.
    Ben-Ari Y, Brody Y, Kinor N, Mor A, Tsukamoto T, Spector DL, Singer RH, Shav-Tal Y (2010) The life of an mRNA in space and time. J Cell Sci 123:1761–1774. doi:10.1242/jcs.062638 CrossRefPubMedPubMedCentralGoogle Scholar
  179. 179.
    Grünwald D, Singer RH, Rout M (2011) Nuclear export dynamics of RNA–protein complexes. Nature 475:333–341. doi:10.1038/nature10318 CrossRefPubMedPubMedCentralGoogle Scholar
  180. 180.
    Kojima S, Green CB (2015) Circadian genomics reveal a role for post-transcriptional regulation in mammals. Biochemistry 54:124–133. doi:10.1021/bi500707c CrossRefPubMedPubMedCentralGoogle Scholar
  181. 181.
    Lunde BM, Moore C, Varani G (2007) RNA-binding proteins: modular design for efficient function. Nat Rev Mol Cell Biol 8:479–490. doi:10.1038/nrm2178 CrossRefPubMedGoogle Scholar
  182. 182.
    Berezikov E (2011) Evolution of microRNA diversity and regulation in animals. Nat Rev Genet 12:846–860. doi:10.1038/nrg3079 CrossRefPubMedGoogle Scholar
  183. 183.
    Jens M, Rajewsky N (2015) Competition between target sites of regulators shapes post-transcriptional gene regulation. Nat Rev Genet 16:113–126. doi:10.1038/nrg3853 CrossRefPubMedGoogle Scholar
  184. 184.
    Sandberg R, Neilson JR, Sarma A, Sharp PA, Burge CB (2008) Proliferating cells express mRNAs with shortened 3′ untranslated regions and fewer microRNA target sites. Science 320:1643–1647. doi:10.1126/science.1155390 CrossRefPubMedPubMedCentralGoogle Scholar
  185. 185.
    Gerstberger S, Hafner M, Tuschl T (2014) A census of human RNA-binding proteins. Nat Rev Genet 15:829–845. doi:10.1038/nrg3813 CrossRefPubMedGoogle Scholar
  186. 186.
    Krol J, Loedige I, Filipowicz W (2010) The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 11:597–610. doi:10.1038/nrg2843 PubMedGoogle Scholar
  187. 187.
    Helwak A, Kudla G, Dudnakova T, Tollervey D (2013) Mapping the human miRNA interactome by CLASH reveals frequent noncanonical binding. Cell 153:654–665. doi:10.1016/j.cell.2013.03.043 CrossRefPubMedPubMedCentralGoogle Scholar
  188. 188.
    Hafner M, Ascano M, Tuschl T (2011) New insights in the mechanism of microRNA-mediated target repression. Nat Struct Mol Biol 18:1181–1182. doi:10.1038/nsmb.2170 CrossRefPubMedPubMedCentralGoogle Scholar
  189. 189.
    Batista PJ, Chang HY (2013) Long noncoding RNAs: cellular address codes in development and disease. Cell 152:1298–1307. doi:10.1016/j.cell.2013.02.012 CrossRefPubMedPubMedCentralGoogle Scholar
  190. 190.
    Berretta J, Morillon A (2009) Pervasive transcription constitutes a new level of eukaryotic genome regulation. EMBO Rep 10:973–982. doi:10.1038/embor.2009.181 CrossRefPubMedPubMedCentralGoogle Scholar
  191. 191.
    Wang ET, Sandberg R, Luo S, Khrebtukova I, Zhang L, Mayr C, Kingsmore S, Schroth GP, Burge CB (2008) Alternative isoform regulation in human tissue transcriptomes. Nature 456:470–476. doi:10.1038/nature07509 CrossRefPubMedPubMedCentralGoogle Scholar
  192. 192.
    Nilsen TW, Graveley BR (2010) Expansion of the eukaryotic proteome by alternative splicing. Nature 463:457–463. doi:10.1038/nature08909 CrossRefPubMedPubMedCentralGoogle Scholar
  193. 193.
    Garneau NL, Wilusz J, Wilusz CJ (2007) The highways and byways of mRNA decay. Nat Rev Mol Cell Biol 8:113–126. doi:10.1038/nrm2104 CrossRefPubMedGoogle Scholar
  194. 194.
    Kojima S, Sher-Chen EL, Green CB (2012) Circadian control of mRNA polyadenylation dynamics regulates rhythmic protein expression. Genes Dev 26:2724–2736. doi:10.1101/gad.208306.112 CrossRefPubMedPubMedCentralGoogle Scholar
  195. 195.
    Dominissini D, Moshitch-Moshkovitz S, Schwartz S, Salmon-Divon M, Ungar L, Osenberg S, Cesarkas K, Jacob-Hirsch J, Amariglio N, Kupiec M, Sorek R, Rechavi G (2012) Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature 485:201–206. doi:10.1038/nature11112 CrossRefPubMedGoogle Scholar
  196. 196.
    Fustin J-M (2013) Doi M, Yamaguchi Y, Hida H, Nishimura S, Yoshida M, Isagawa T, Morioka MS, Kakeya H, Manabe I, Okamura H RNA-methylation-dependent RNA processing controls the speed of the circadian clock. Cell 155:793–806. doi:10.1016/j.cell.2013.10.026 CrossRefPubMedGoogle Scholar
  197. 197.
    Robinson BG, Frim DM, Schwartz WJ, Majzoub JA (1988) Vasopressin mRNA in the suprachiasmatic nuclei: daily regulation of polyadenylate tail length. Science 241:342–344CrossRefPubMedGoogle Scholar
  198. 198.
    So WV, Rosbash M (1997) Post-transcriptional regulation contributes to Drosophila clock gene mRNA cycling. EMBO J 16:7146–7155. doi:10.1093/emboj/16.23.7146 CrossRefPubMedPubMedCentralGoogle Scholar
  199. 199.
    Cheng Y, Gvakharia B, Hardin PE (1998) Two alternatively spliced transcripts from the Drosophila period gene rescue rhythms having different molecular and behavioral characteristics. Mol Cell Biol 18:6505–6514CrossRefPubMedPubMedCentralGoogle Scholar
  200. 200.
    Majercak J, Sidote D, Hardin PE, Edery I (1999) How a circadian clock adapts to seasonal decreases in temperature and day length. Neuron 24:219–230. doi:10.1016/S0896-6273(00)80834-X CrossRefPubMedGoogle Scholar
  201. 201.
    Kwak E, Kim T-D, Kim K-T (2006) Essential role of 3′-untranslated region-mediated mRNA decay in circadian oscillations of mouse Period3 mRNA. J Biol Chem 281:19100–19106. doi:10.1074/jbc.M511927200 CrossRefPubMedGoogle Scholar
  202. 202.
    Woo K-C, Kim T-D, Lee K-H, Kim D-Y, Kim W, Lee K-Y, Kim K-T (2009) Mouse period 2 mRNA circadian oscillation is modulated by PTB–mediated rhythmic mRNA degradation. Nucleic Acids Res 37:26–37. doi:10.1093/nar/gkn893 CrossRefPubMedPubMedCentralGoogle Scholar
  203. 203.
    Woo K-C, Ha D-C, Lee K-H, Kim D-Y, Kim T-D, Kim K-T (2010) Circadian amplitude of cryptochrome 1 is modulated by mRNA stability regulation via cytoplasmic hnRNP D oscillation. Mol Cell Biol 30:197–205. doi:10.1128/MCB.01154-09 CrossRefPubMedPubMedCentralGoogle Scholar
  204. 204.
    Wang Y, Osterbur DL, Megaw PL, Tosini G, Fukuhara C, Green CB, Besharse JC (2001) Rhythmic expression of Nocturnin mRNA in multiple tissues of the mouse. BMC Dev Biol 1:9CrossRefPubMedPubMedCentralGoogle Scholar
  205. 205.
    Stubblefield JJ, Terrien J, Green CB (2012) Nocturnin: at the crossroads of clocks and metabolism. Trends Endocrinol Metab 23:326–333. doi:10.1016/j.tem.2012.03.007 CrossRefPubMedPubMedCentralGoogle Scholar
  206. 206.
    Godwin AR, Kojima S, Green CB, Wilusz J (2013) Kiss your tail goodbye: the role of PARN, Nocturnin, and Angel deadenylases in mRNA biology. Biochim Biophys Acta BBA - Gene Regul Mech 1829:571–579. doi:10.1016/j.bbagrm.2012.12.004 CrossRefGoogle Scholar
  207. 207.
    Kojima S, Matsumoto K, Hirose M, Shimada M, Nagano M, Shigeyoshi Y, Hoshino S, Ui-Tei K, Saigo K, Green CB, Sakaki Y, Tei H (2007) LARK activates posttranscriptional expression of an essential mammalian clock protein, PERIOD1. Proc Natl Acad Sci 104:1859–1864. doi:10.1073/pnas.0607567104 CrossRefPubMedPubMedCentralGoogle Scholar
  208. 208.
    Markus MA, Morris BJ (2009) RBM4: a multifunctional RNA-binding protein. Int J Biochem Cell Biol 41:740–743. doi:10.1016/j.biocel.2008.05.027 CrossRefPubMedGoogle Scholar
  209. 209.
    Newby LM, Jackson FR (1996) Regulation of a specific circadian clock output pathway by lark, a putative RNA-binding protein with repressor activity. J Neurobiol 31:117–128. doi:10.1002/(SICI)1097-4695(199609)31:1<117:AID-NEU10>3.0.CO;2-I CrossRefPubMedGoogle Scholar
  210. 210.
    Myers EM, Yu J, Sehgal A (2003) Circadian control of eclosion: interaction between a central and peripheral clock in Drosophila melanogaster. Curr Biol 13:526–533CrossRefPubMedGoogle Scholar
  211. 211.
    Keene JD (2007) Biological clocks and the coordination theory of RNA operons and regulons. Cold Spring Harb Symp Quant Biol 72:157–165. doi:10.1101/sqb.2007.72.013 CrossRefPubMedGoogle Scholar
  212. 212.
    Menet JS, Rodriguez J, Abruzzi KC, Rosbash M (2012) Nascent-Seq reveals novel features of mouse circadian transcriptional regulation. eLife 1:e00011–e00011. doi: 10.7554/eLife.00011
  213. 213.
    Doherty CJ, Kay SA (2012) Circadian surprise—it’s not all about transcription. Science 338:338–340. doi:10.1126/science.1230008 CrossRefPubMedGoogle Scholar
  214. 214.
    Rodriguez J, Tang C-HA, Khodor YL, Vodala S, Menet JS, Rosbash M (2013) Nascent-Seq analysis of Drosophila cycling gene expression. Proc Natl Acad Sci 110:E275–E284. doi:10.1073/pnas.1219969110 CrossRefPubMedPubMedCentralGoogle Scholar
  215. 215.
    Morf J, Rey G, Schneider K, Stratmann M, Fujita J, Naef F, Schibler U (2012) Cold-inducible RNA-binding protein modulates circadian gene expression posttranscriptionally. Science 338:379–383. doi:10.1126/science.1217726 CrossRefPubMedGoogle Scholar
  216. 216.
    Liu Y, Hu W, Murakawa Y, Yin J, Wang G, Landthaler M, Yan J (2013) Cold-induced RNA-binding proteins regulate circadian gene expression by controlling alternative polyadenylation. Sci Rep 3:2054. doi:10.1038/srep02054 PubMedPubMedCentralGoogle Scholar
  217. 217.
    McGlincy NJ, Valomon A, Chesham JE, Maywood ES, Hastings MH, Ule J (2012) Regulation of alternative splicing by the circadian clock and food related cues. Genome Biol 13:R54. doi:10.1186/gb-2012-13-6-r54 CrossRefPubMedPubMedCentralGoogle Scholar
  218. 218.
    Gatfield D, Le Martelot G, Vejnar CE, Gerlach D, Schaad O, Fleury-Olela F, Ruskeepää A-L, Oresic M, Esau CC, Zdobnov EM, Schibler U (2009) Integration of microRNA miR-122 in hepatic circadian gene expression. Genes Dev 23:1313–1326. doi:10.1101/gad.1781009 CrossRefPubMedPubMedCentralGoogle Scholar
  219. 219.
    Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T (2002) Identification of tissue-specific microRNAs from mouse. Curr Biol 12:735–739. doi:10.1016/S0960-9822(02)00809-6 CrossRefPubMedGoogle Scholar
  220. 220.
    Krützfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, Stoffel M (2005) Silencing of microRNAs in vivo with “antagomirs”. Nature 438:685–689. doi:10.1038/nature04303 CrossRefPubMedGoogle Scholar
  221. 221.
    Esau C, Davis S, Murray SF, Yu XX, Pandey SK, Pear M, Watts L, Booten SL, Graham M, McKay R, Subramaniam A, Propp S, Lollo BA, Freier S, Bennett CF, Bhanot S, Monia BP (2006) miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab 3:87–98. doi:10.1016/j.cmet.2006.01.005 CrossRefPubMedGoogle Scholar
  222. 222.
    Vodala S, Pescatore S, Rodriguez J, Buescher M, Chen Y-W, Weng R, Cohen SM, Rosbash M (2012) The oscillating miRNA 959-964 cluster impacts Drosophila feeding time and other circadian outputs. Cell Metab 16:601–612. doi:10.1016/j.cmet.2012.10.002 CrossRefPubMedPubMedCentralGoogle Scholar
  223. 223.
    Du N-H, Arpat AB, Matos MD, Gatfield D (2014) MicroRNAs shape circadian hepatic gene expression on a transcriptome-wide scale. eLife. doi:10.7554/eLife.02510 PubMedCentralGoogle Scholar
  224. 224.
    Hausser J, Syed AP, Selevsek N, van Nimwegen E, Jaskiewicz L, Aebersold R, Zavolan M (2014) Timescales and bottlenecks in miRNA-dependent gene regulation. Mol Syst Biol 9:711–712. doi:10.1038/msb.2013.68 CrossRefGoogle Scholar
  225. 225.
    Keene JD (2007) RNA regulons: coordination of post-transcriptional events. Nat Rev Genet 8:533–543. doi:10.1038/nrg2111 CrossRefPubMedGoogle Scholar
  226. 226.
    Moore MJ (2005) From birth to death: the complex lives of eukaryotic mRNAs. Science 309:1514–1518. doi:10.1126/science.1111443 CrossRefPubMedGoogle Scholar
  227. 227.
    Castello A, Fischer B, Eichelbaum K, Horos R, Beckmann BM, Strein C, Davey NE, Humphreys DT, Preiss T, Steinmetz LM, Krijgsveld J, Hentze MW (2012) Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 149:1393–1406. doi:10.1016/j.cell.2012.04.031 CrossRefPubMedGoogle Scholar
  228. 228.
    Kwon SC, Yi H, Eichelbaum K, Föhr S, Fischer B, You KT, Castello A, Krijgsveld J, Hentze MW, Kim VN (2013) The RNA-binding protein repertoire of embryonic stem cells. Nat Struct Mol Biol 20:1122–1130. doi:10.1038/nsmb.2638 CrossRefPubMedGoogle Scholar
  229. 229.
    Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233. doi:10.1016/j.cell.2009.01.002 CrossRefPubMedPubMedCentralGoogle Scholar
  230. 230.
    Ouyang Y, Andersson CR, Kondo T, Golden SS, Johnson CH (1998) Resonating circadian clocks enhance fitness in cyanobacteria. Proc Natl Acad Sci 95:8660–8664CrossRefPubMedPubMedCentralGoogle Scholar
  231. 231.
    Dodd AN, Salathia N, Hall A, Kévei E, Tóth R, Nagy F, Hibberd JM, Millar AJ, Webb AAR (2005) Plant circadian clocks increase photosynthesis, growth, survival, and competitive advantage. Science 309:630–633. doi:10.1126/science.1115581 CrossRefPubMedGoogle Scholar
  232. 232.
    Antoch MP, Kondratov RV (2010) Circadian proteins and genotoxic stress response. Circ Res 106:68–78. doi:10.1161/CIRCRESAHA.109.207076 CrossRefPubMedGoogle Scholar
  233. 233.
    Pittendrigh CS, Minis DH (1972) Circadian systems: longevity as a function of circadian resonance in Drosophila melanogaster. Proc Natl Acad Sci 69:1537–1539CrossRefPubMedPubMedCentralGoogle Scholar
  234. 234.
    Wyse CA, Coogan AN, Selman C, Hazlerigg DG, Speakman JR (2010) Association between mammalian lifespan and circadian free-running period: the circadian resonance hypothesis revisited. Biol Lett 6:696–698. doi:10.1098/rsbl.2010.0152 CrossRefPubMedPubMedCentralGoogle Scholar
  235. 235.
    Mitchell A, Romano GH, Groisman B, Yona A, Dekel E, Kupiec M, Dahan O, Pilpel Y (2009) Adaptive prediction of environmental changes by microorganisms. Nature 460:220–224. doi:10.1038/nature08112 CrossRefPubMedGoogle Scholar
  236. 236.
    Dhar R, Sägesser R, Weikert C, Wagner A (2013) Yeast adapts to a changing stressful environment by evolving cross-protection and anticipatory gene regulation. Mol Biol Evol 30:573–588. doi:10.1093/molbev/mss253 CrossRefPubMedGoogle Scholar
  237. 237.
    Klevecz RR, Bolen J, Forrest G, Murray DB (2004) A genomewide oscillation in transcription gates DNA replication and cell cycle.  Proc Natl Acad Sci 101:1200–1205. doi: 10.1073/pnas.0306490101 CrossRefPubMedPubMedCentralGoogle Scholar
  238. 238.
    Sachdeva UM, Thompson CB (2008) Diurnal rhythms of autophagy: implications for cell biology and human disease. Autophagy 4:581–589CrossRefPubMedGoogle Scholar
  239. 239.
    Borgs L, Beukelaers P, Vandenbosch R, Belachew S, Nguyen L, Malgrange B (2009) Cell “circadian” cycle: new role for mammalian core clock genes. Cell Cycle 8:832–837CrossRefPubMedGoogle Scholar
  240. 240.
    Kondratova AA, Kondratov RV (2012) The circadian clock and pathology of the ageing brain. Nat Rev Neurosci 13:325–335. doi:10.1038/nrn3208 PubMedPubMedCentralGoogle Scholar
  241. 241.
    Mauvoisin D, Wang J, Jouffe C, Martin E, Atger F, Waridel P, Quadroni M, Gachon F, Naef F (2014) Circadian clock-dependent and -independent rhythmic proteomes implement distinct diurnal functions in mouse liver. Proc Natl Acad Sci 111:167–172. doi:10.1073/pnas.1314066111 CrossRefPubMedPubMedCentralGoogle Scholar
  242. 242.
    Cox J, Mann M (2011) Quantitative, high-resolution proteomics for data-driven systems biology. Annu Rev Biochem 80:273–299. doi:10.1146/annurev-biochem-061308-093216 CrossRefPubMedGoogle Scholar
  243. 243.
    Mauvoisin D, Dayon L, Gachon F, Kussmann M (2015) Proteomics and circadian rhythms: it’s all about signaling! Proteomics 15:310–317. doi:10.1002/pmic.201400187 CrossRefPubMedPubMedCentralGoogle Scholar
  244. 244.
    Durgan DJ, Pat BM, Laczy B, Bradley JA, Tsai J-Y, Grenett MH, Ratcliffe WF, Brewer RA, Nagendran J, Villegas-Montoya C, Zou C, Zou L, Johnson RL, Dyck JRB, Bray MS, Gamble KL, Chatham JC, Young ME (2011) O-GlcNAcylation, novel post-translational modification linking myocardial metabolism and cardiomyocyte circadian clock. J Biol Chem 286:44606–44619. doi:10.1074/jbc.M111.278903 CrossRefPubMedPubMedCentralGoogle Scholar
  245. 245.
    Kim EY, Jeong EH, Park S, Jeong H-J, Edery I, Cho JW (2012) A role for O-GlcNAcylation in setting circadian clock speed. Genes Dev 26:490–502. doi:10.1101/gad.182378.111 CrossRefPubMedPubMedCentralGoogle Scholar
  246. 246.
    Kaasik K, Kivimäe S, Allen JJ, Chalkley RJ, Huang Y, Baer K, Kissel H, Burlingame AL, Shokat KM, Ptáček LJ, Fu Y-H (2013) Glucose sensor O-GlcNAcylation coordinates with phosphorylation to regulate circadian clock. Cell Metab 17:291–302. doi:10.1016/j.cmet.2012.12.017 CrossRefPubMedPubMedCentralGoogle Scholar
  247. 247.
    Li M-D, Ruan H-B, Hughes ME, Lee J-S, Singh JP, Jones SP, Nitabach MN, Yang X (2013) O-GlcNAc signaling entrains the circadian clock by inhibiting BMAL1/CLOCK ubiquitination. Cell Metab 17:303–310. doi:10.1016/j.cmet.2012.12.015 CrossRefPubMedPubMedCentralGoogle Scholar
  248. 248.
    Weatheritt RJ, Gibson TJ, Babu MM (2014) Asymmetric mRNA localization contributes to fidelity and sensitivity of spatially localized systems. Nat Struct Mol Biol 21:833–839. doi:10.1038/nsmb.2876 CrossRefPubMedPubMedCentralGoogle Scholar
  249. 249.
    Dai M, Wang P, Boyd AD, Kostov G, Athey B, Jones EG, Bunney WE, Myers RM, Speed TP, Akil H, Watson SJ, Meng F (2005) Evolving gene/transcript definitions significantly alter the interpretation of GeneChip data. Nucleic Acids Res 33:e175–e175. doi:10.1093/nar/gni179 CrossRefPubMedPubMedCentralGoogle Scholar
  250. 250.
    Durinck S, Spellman PT, Birney E, Huber W (2009) Mapping identifiers for the integration of genomic datasets with the R/Bioconductor package biomaRt. Nat Protoc 4:1184–1191. doi:10.1038/nprot.2009.97 CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer Basel 2015

Authors and Affiliations

  1. 1.Institute for Theoretical BiologyCharité – Universitätsmedizin BerlinBerlinGermany

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