Clock

Summary

Gene Symbol: Clock
Description: circadian locomotor output cycles kaput
Alias: 5330400M04Rik, KAT13D, circadian locomoter output cycles protein kaput
Species: mouse
Products:     Clock

Top Publications

  1. Antoch M, Song E, Chang A, Vitaterna M, Zhao Y, Wilsbacher L, et al. Functional identification of the mouse circadian Clock gene by transgenic BAC rescue. Cell. 1997;89:655-67 pubmed
    ..with bacterial artificial chromosome (BAC) clones expressed in transgenic mice to identify the circadian Clock gene...
  2. Pitts S, Perone E, Silver R. Food-entrained circadian rhythms are sustained in arrhythmic Clk/Clk mutant mice. Am J Physiol Regul Integr Comp Physiol. 2003;285:R57-67 pubmed
    ..Circadian rhythms within the SCN depend on transcription-translation feedback loops in which CLOCK protein is a key positive regulator...
  3. Marcheva B, Ramsey K, Buhr E, Kobayashi Y, Su H, Ko C, et al. Disruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes. Nature. 2010;466:627-31 pubmed publisher
    The molecular clock maintains energy constancy by producing circadian oscillations of rate-limiting enzymes involved in tissue metabolism across the day and night...
  4. Lee C, Weaver D, Reppert S. Direct association between mouse PERIOD and CKIepsilon is critical for a functioning circadian clock. Mol Cell Biol. 2004;24:584-94 pubmed
    The mPER1 and mPER2 proteins have important roles in the circadian clock mechanism, whereas mPER3 is expendable...
  5. Nakahata Y, Sahar S, Astarita G, Kaluzova M, Sassone Corsi P. Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1. Science. 2009;324:654-7 pubmed publisher
    ..We have shown that the core circadian regulator, CLOCK, is a histone acetyltransferase whose activity is counterbalanced by the nicotinamide adenine dinucleotide (NAD+)-..
  6. Oishi K, Miyazaki K, Kadota K, Kikuno R, Nagase T, Atsumi G, et al. Genome-wide expression analysis of mouse liver reveals CLOCK-regulated circadian output genes. J Biol Chem. 2003;278:41519-27 pubmed
    b>CLOCK is a positive component of a transcription/translation-based negative feedback loop of the central circadian oscillator in the suprachiasmatic nucleus in mammals...
  7. Bertolucci C, Cavallari N, Colognesi I, Aguzzi J, Chen Z, Caruso P, et al. Evidence for an overlapping role of CLOCK and NPAS2 transcription factors in liver circadian oscillators. Mol Cell Biol. 2008;28:3070-5 pubmed publisher
    ..levels oscillate in a circadian manner and its promoter contains E-boxes, which are putative DNA-binding sites for CLOCK-BMAL1 and NPAS2-BMAL1 heterodimers and hallmarks of circadian regulation...
  8. Kozlov S, Bogenpohl J, Howell M, Wevrick R, Panda S, Hogenesch J, et al. The imprinted gene Magel2 regulates normal circadian output. Nat Genet. 2007;39:1266-72 pubmed
    ..robust rhythmicity of Magel2 expression in the SCN and the altered behavioral rhythmicity of null mice reveal Magel2 to be a clock-controlled circadian output gene whose disruption results in some of the phenotypes characteristic of PWS.
  9. Ripperger J, Schibler U. Rhythmic CLOCK-BMAL1 binding to multiple E-box motifs drives circadian Dbp transcription and chromatin transitions. Nat Genet. 2006;38:369-74 pubmed
    ..Essentially, the activity of the transcription factors BMAL1 (also known as MOP3) and CLOCK is rhythmically counterbalanced by Period (PER) and Cryptochrome (CRY) proteins to govern time of day-dependent ..
  10. Sato T, Yamada R, Ukai H, Baggs J, Miraglia L, Kobayashi T, et al. Feedback repression is required for mammalian circadian clock function. Nat Genet. 2006;38:312-9 pubmed
    Direct evidence for the requirement of transcriptional feedback repression in circadian clock function has been elusive...

Detail Information

Publications78

  1. Antoch M, Song E, Chang A, Vitaterna M, Zhao Y, Wilsbacher L, et al. Functional identification of the mouse circadian Clock gene by transgenic BAC rescue. Cell. 1997;89:655-67 pubmed
    ..with bacterial artificial chromosome (BAC) clones expressed in transgenic mice to identify the circadian Clock gene...
  2. Pitts S, Perone E, Silver R. Food-entrained circadian rhythms are sustained in arrhythmic Clk/Clk mutant mice. Am J Physiol Regul Integr Comp Physiol. 2003;285:R57-67 pubmed
    ..Circadian rhythms within the SCN depend on transcription-translation feedback loops in which CLOCK protein is a key positive regulator...
  3. Marcheva B, Ramsey K, Buhr E, Kobayashi Y, Su H, Ko C, et al. Disruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes. Nature. 2010;466:627-31 pubmed publisher
    The molecular clock maintains energy constancy by producing circadian oscillations of rate-limiting enzymes involved in tissue metabolism across the day and night...
  4. Lee C, Weaver D, Reppert S. Direct association between mouse PERIOD and CKIepsilon is critical for a functioning circadian clock. Mol Cell Biol. 2004;24:584-94 pubmed
    The mPER1 and mPER2 proteins have important roles in the circadian clock mechanism, whereas mPER3 is expendable...
  5. Nakahata Y, Sahar S, Astarita G, Kaluzova M, Sassone Corsi P. Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1. Science. 2009;324:654-7 pubmed publisher
    ..We have shown that the core circadian regulator, CLOCK, is a histone acetyltransferase whose activity is counterbalanced by the nicotinamide adenine dinucleotide (NAD+)-..
  6. Oishi K, Miyazaki K, Kadota K, Kikuno R, Nagase T, Atsumi G, et al. Genome-wide expression analysis of mouse liver reveals CLOCK-regulated circadian output genes. J Biol Chem. 2003;278:41519-27 pubmed
    b>CLOCK is a positive component of a transcription/translation-based negative feedback loop of the central circadian oscillator in the suprachiasmatic nucleus in mammals...
  7. Bertolucci C, Cavallari N, Colognesi I, Aguzzi J, Chen Z, Caruso P, et al. Evidence for an overlapping role of CLOCK and NPAS2 transcription factors in liver circadian oscillators. Mol Cell Biol. 2008;28:3070-5 pubmed publisher
    ..levels oscillate in a circadian manner and its promoter contains E-boxes, which are putative DNA-binding sites for CLOCK-BMAL1 and NPAS2-BMAL1 heterodimers and hallmarks of circadian regulation...
  8. Kozlov S, Bogenpohl J, Howell M, Wevrick R, Panda S, Hogenesch J, et al. The imprinted gene Magel2 regulates normal circadian output. Nat Genet. 2007;39:1266-72 pubmed
    ..robust rhythmicity of Magel2 expression in the SCN and the altered behavioral rhythmicity of null mice reveal Magel2 to be a clock-controlled circadian output gene whose disruption results in some of the phenotypes characteristic of PWS.
  9. Ripperger J, Schibler U. Rhythmic CLOCK-BMAL1 binding to multiple E-box motifs drives circadian Dbp transcription and chromatin transitions. Nat Genet. 2006;38:369-74 pubmed
    ..Essentially, the activity of the transcription factors BMAL1 (also known as MOP3) and CLOCK is rhythmically counterbalanced by Period (PER) and Cryptochrome (CRY) proteins to govern time of day-dependent ..
  10. Sato T, Yamada R, Ukai H, Baggs J, Miraglia L, Kobayashi T, et al. Feedback repression is required for mammalian circadian clock function. Nat Genet. 2006;38:312-9 pubmed
    Direct evidence for the requirement of transcriptional feedback repression in circadian clock function has been elusive...
  11. Ozber N, Baris I, Tatlici G, Gur I, Kilinc S, Unal E, et al. Identification of two amino acids in the C-terminal domain of mouse CRY2 essential for PER2 interaction. BMC Mol Biol. 2010;11:69 pubmed publisher
    ..They also act as integral parts of the central circadian oscillator in humans and other animals. In mammals, the CLOCK-BMAL1 heterodimer activates transcription of the Per and Cry genes as well as clock-regulated genes...
  12. Lee Y, Lee J, Kwon I, Nakajima Y, Ohmiya Y, Son G, et al. Coactivation of the CLOCK-BMAL1 complex by CBP mediates resetting of the circadian clock. J Cell Sci. 2010;123:3547-57 pubmed publisher
    The transcription factor CLOCK-BMAL1 is a core component of the molecular clock machinery that drives circadian gene expression and physiology in mammals...
  13. Honma S, Kawamoto T, Takagi Y, Fujimoto K, Sato F, Noshiro M, et al. Dec1 and Dec2 are regulators of the mammalian molecular clock. Nature. 2002;419:841-4 pubmed
    ..Four clock-gene families have been found to be involved in a transcription-translation feedback loop that generates the ..
  14. Wyse C, Coogan A. Impact of aging on diurnal expression patterns of CLOCK and BMAL1 in the mouse brain. Brain Res. 2010;1337:21-31 pubmed publisher
    ..rhythms are generated by a network of transcriptional and translational loops in the expression of a panel of clock genes in various brain and peripheral sites...
  15. Bray M, Shaw C, Moore M, Garcia R, Zanquetta M, Durgan D, et al. Disruption of the circadian clock within the cardiomyocyte influences myocardial contractile function, metabolism, and gene expression. Am J Physiol Heart Circ Physiol. 2008;294:H1036-47 pubmed
    Virtually every mammalian cell, including cardiomyocytes, possesses an intrinsic circadian clock. The role of this transcriptionally based molecular mechanism in cardiovascular biology is poorly understood...
  16. Beaule C, Cheng H. The acetyltransferase Clock is dispensable for circadian aftereffects in mice. J Biol Rhythms. 2011;26:561-4 pubmed publisher
    Recent demonstration of the histone acetyltransferase activity of the Clock gene greatly expanded the regulatory role of circadian clocks in gene transcription...
  17. King D, Vitaterna M, Chang A, Dove W, Pinto L, Turek F, et al. The mouse Clock mutation behaves as an antimorph and maps within the W19H deletion, distal of Kit. Genetics. 1997;146:1049-60 pubmed
    b>Clock is a semidominant mutation identified from an N-ethyl-N-nitrosourea mutagenesis screen in mice...
  18. Ochi M, Sono S, Sei H, Oishi K, Kobayashi H, Morita Y, et al. Sex difference in circadian period of body temperature in Clock mutant mice with Jcl/ICR background. Neurosci Lett. 2003;347:163-6 pubmed
    ..We observed that the free-running period of core body temperature is longer in male homozygous Clock mutant mice than in females, although this difference is not found in wild mice...
  19. Zhao W, Malinin N, Yang F, Staknis D, Gekakis N, Maier B, et al. CIPC is a mammalian circadian clock protein without invertebrate homologues. Nat Cell Biol. 2007;9:268-75 pubmed
    At the core of the mammalian circadian clock is a feedback loop in which the heterodimeric transcription factor CLOCK-Brain, Muscle Arnt-like-1 (BMAL1) drives expression of its negative regulators, periods (PERs) and cryptochromes (CRYs)...
  20. Cretenet G, Le Clech M, Gachon F. Circadian clock-coordinated 12 Hr period rhythmic activation of the IRE1alpha pathway controls lipid metabolism in mouse liver. Cell Metab. 2010;11:47-57 pubmed publisher
    The mammalian circadian clock plays a fundamental role in the liver by regulating fatty acid, glucose, and xenobiotic metabolism. Impairment of this rhythm has been shown to lead to diverse pathologies, including metabolic syndrome...
  21. Westgate E, Cheng Y, Reilly D, Price T, Walisser J, Bradfield C, et al. Genetic components of the circadian clock regulate thrombogenesis in vivo. Circulation. 2008;117:2087-95 pubmed publisher
    ..genes relevant to hemostasis and vascular integrity undergo circadian oscillation, the role of the molecular clock in thrombotic events remains to be established...
  22. Eckel Mahan K, Patel V, Mohney R, Vignola K, Baldi P, Sassone Corsi P. Coordination of the transcriptome and metabolome by the circadian clock. Proc Natl Acad Sci U S A. 2012;109:5541-6 pubmed publisher
    The circadian clock governs a large array of physiological functions through the transcriptional control of a significant fraction of the genome. Disruption of the clock leads to metabolic disorders, including obesity and diabetes...
  23. Duong H, Robles M, Knutti D, Weitz C. A molecular mechanism for circadian clock negative feedback. Science. 2011;332:1436-9 pubmed publisher
    ..in which the three PERIOD (PER) proteins, acting in a large complex, inhibit the transcriptional activity of the CLOCK-BMAL1 dimer, which represses their own expression...
  24. Curtis A, Seo S, Westgate E, Rudic R, Smyth E, Chakravarti D, et al. Histone acetyltransferase-dependent chromatin remodeling and the vascular clock. J Biol Chem. 2004;279:7091-7 pubmed
    ..coactivators and histone acetyltransferases, p300/CBP, PCAF, and ACTR associate with the bHLH-PAS proteins, CLOCK and NPAS2, to regulate positively clock gene expression...
  25. Sujino M, Masumoto K, Yamaguchi S, van der Horst G, Okamura H, Inouye S. Suprachiasmatic nucleus grafts restore circadian behavioral rhythms of genetically arrhythmic mice. Curr Biol. 2003;13:664-8 pubmed
    The mammalian master clock driving circadian rhythmicity in physiology and behavior resides within the suprachiasmatic nuclei (SCN) of the hypothalamus...
  26. Huang N, Chelliah Y, Shan Y, Taylor C, Yoo S, PARTCH C, et al. Crystal structure of the heterodimeric CLOCK:BMAL1 transcriptional activator complex. Science. 2012;337:189-94 pubmed publisher
    The circadian clock in mammals is driven by an autoregulatory transcriptional feedback mechanism that takes approximately 24 hours to complete...
  27. Yujnovsky I, Hirayama J, Doi M, Borrelli E, Sassone Corsi P. Signaling mediated by the dopamine D2 receptor potentiates circadian regulation by CLOCK:BMAL1. Proc Natl Acad Sci U S A. 2006;103:6386-91 pubmed
    ..of intracellular pathways whose signaling is integrated by the molecular mechanism that constitutes the circadian clock. Although the essential gears of the circadian machinery have been elucidated, very little is known about the ..
  28. Amano T, Matsushita A, Hatanaka Y, Watanabe T, Oishi K, Ishida N, et al. Expression and functional analyses of circadian genes in mouse oocytes and preimplantation embryos: Cry1 is involved in the meiotic process independently of circadian clock regulation. Biol Reprod. 2009;80:473-83 pubmed publisher
    In mammals, circadian genes, Clock, Arntl (also known as Bmal1), Cry1, Cry2, Per1, Per2, and Per3, are rhythmically transcribed every 24 h in almost all organs and tissues to tick the circadian clock...
  29. Herzog E, Takahashi J, Block G. Clock controls circadian period in isolated suprachiasmatic nucleus neurons. Nat Neurosci. 1998;1:708-13 pubmed
    ..SCN) is the master circadian pacemaker in mammals, and one molecular regulator of circadian rhythms is the Clock gene. Here we studied the discharge patterns of SCN neurons isolated from Clock mutant mice...
  30. Hirayama J, Sahar S, Grimaldi B, Tamaru T, Takamatsu K, Nakahata Y, et al. CLOCK-mediated acetylation of BMAL1 controls circadian function. Nature. 2007;450:1086-90 pubmed
    ..The CLOCK-BMAL1 complex activates clock-controlled genes, including cryptochromes (Crys), the products of which act as ..
  31. Sei H, Oishi K, Morita Y, Ishida N. Mouse model for morningness/eveningness. Neuroreport. 2001;12:1461-4 pubmed
    ..preferences has recently been reported to be associated with polymorphism of the 3' flanking region of the Clock gene, which was the first identified mammalian circadian clock gene...
  32. Jin X, Shearman L, Weaver D, Zylka M, de Vries G, Reppert S. A molecular mechanism regulating rhythmic output from the suprachiasmatic circadian clock. Cell. 1999;96:57-68 pubmed
    We examined the transcriptional regulation of the clock-controlled arginine vasopressin gene in the suprachiasmatic nuclei (SCN)...
  33. Kondratov R, Shamanna R, Kondratova A, Gorbacheva V, Antoch M. Dual role of the CLOCK/BMAL1 circadian complex in transcriptional regulation. FASEB J. 2006;20:530-2 pubmed
    The basic helix-loop-helix (bHLH) -PAS domain containing transcription factors CLOCK and BMAL1 are two major components of the circadian molecular oscillator...
  34. Lee C, Etchegaray J, Cagampang F, Loudon A, Reppert S. Posttranslational mechanisms regulate the mammalian circadian clock. Cell. 2001;107:855-67 pubmed
    We have examined posttranslational regulation of clock proteins in mouse liver in vivo. The mouse PERIOD proteins (mPER1 and mPER2), CLOCK, and BMAL1 undergo robust circadian changes in phosphorylation...
  35. Katada S, Sassone Corsi P. The histone methyltransferase MLL1 permits the oscillation of circadian gene expression. Nat Struct Mol Biol. 2010;17:1414-21 pubmed publisher
    The classical view of the molecular clock is based on interlocked transcriptional-translational feedback loops...
  36. Rudic R, McNamara P, Curtis A, Boston R, Panda S, Hogenesch J, et al. BMAL1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasis. PLoS Biol. 2004;2:e377 pubmed
    Circadian timing is generated through a unique series of autoregulatory interactions termed the molecular clock. Behavioral rhythms subject to the molecular clock are well characterized...
  37. Debruyne J, Weaver D, Reppert S. CLOCK and NPAS2 have overlapping roles in the suprachiasmatic circadian clock. Nat Neurosci. 2007;10:543-5 pubmed
    Heterodimers of CLOCK and BMAL1, bHLH-PAS transcription factors, are believed to be the major transcriptional regulators of the circadian clock mechanism in mammals...
  38. Nakahata Y, Kaluzova M, Grimaldi B, Sahar S, Hirayama J, Chen D, et al. The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control. Cell. 2008;134:329-40 pubmed publisher
    Circadian rhythms govern a large array of metabolic and physiological functions. The central clock protein CLOCK has HAT properties...
  39. Shearman L, Sriram S, Weaver D, Maywood E, Chaves I, Zheng B, et al. Interacting molecular loops in the mammalian circadian clock. Science. 2000;288:1013-9 pubmed
    We show that, in the mouse, the core mechanism for the master circadian clock consists of interacting positive and negative transcription and translation feedback loops...
  40. Kwon I, Lee J, Chang S, Jung N, Lee B, Son G, et al. BMAL1 shuttling controls transactivation and degradation of the CLOCK/BMAL1 heterodimer. Mol Cell Biol. 2006;26:7318-30 pubmed
    b>CLOCK and BMAL1 are bHLH-PAS-containing transcription factors that bind to E-box elements and are indispensable for expression of core circadian clock components such as the Per and Cry genes...
  41. Dolatshad H, Campbell E, O HARA L, Maywood E, Hastings M, Johnson M. Developmental and reproductive performance in circadian mutant mice. Hum Reprod. 2006;21:68-79 pubmed
    ..We compare fecundity in Clock(Delta19) mutant mice (a dominant-negative protein essential for circadian rhythm activity) and in Vipr2-/- null ..
  42. Ye R, Selby C, Ozturk N, Annayev Y, Sancar A. Biochemical analysis of the canonical model for the mammalian circadian clock. J Biol Chem. 2011;286:25891-902 pubmed publisher
    The current consensus model for the circadian clock in mammals is based on a transcription-translation feedback loop...
  43. Miki T, Xu Z, Chen Goodspeed M, Liu M, Van Oort Jansen A, Rea M, et al. PML regulates PER2 nuclear localization and circadian function. EMBO J. 2012;31:1427-39 pubmed publisher
    Studies have suggested that the clock regulator PER2 is a tumour suppressor. A cancer network involving PER2 raises the possibility that some tumour suppressors are directly involved in the mammalian clock...
  44. Low Zeddies S, Takahashi J. Chimera analysis of the Clock mutation in mice shows that complex cellular integration determines circadian behavior. Cell. 2001;105:25-42 pubmed
    The Clock mutation lengthens periodicity and reduces amplitude of circadian rhythms in mice. The effects of Clock are cell intrinsic and can be observed at the level of single neurons in the suprachiasmatic nucleus...
  45. King D, Zhao Y, Sangoram A, Wilsbacher L, Tanaka M, Antoch M, et al. Positional cloning of the mouse circadian clock gene. Cell. 1997;89:641-53 pubmed
    We used positional cloning to identify the circadian Clock gene in mice. Clock is a large transcription unit with 24 exons spanning approximately 100,000 bp of DNA from which transcript classes of 7.5 and approximately 10 kb arise...
  46. Kondratov R, Chernov M, Kondratova A, Gorbacheva V, Gudkov A, Antoch M. BMAL1-dependent circadian oscillation of nuclear CLOCK: posttranslational events induced by dimerization of transcriptional activators of the mammalian clock system. Genes Dev. 2003;17:1921-32 pubmed
    Mammalian CLOCK and BMAL1 are two members of bHLH-PAS-containing family of transcription factors that represent the positive elements of circadian autoregulatory feedback loop...
  47. Kudo T, Kawashima M, Tamagawa T, Shibata S. Clock mutation facilitates accumulation of cholesterol in the liver of mice fed a cholesterol and/or cholic acid diet. Am J Physiol Endocrinol Metab. 2008;294:E120-30 pubmed
    ..Since a circadian clock controls the gene expression of these enzymes, these genes exhibit circadian rhythm in the liver...
  48. Cheng M, Bullock C, Li C, Lee A, Bermak J, Belluzzi J, et al. Prokineticin 2 transmits the behavioural circadian rhythm of the suprachiasmatic nucleus. Nature. 2002;417:405-10 pubmed
    ..prokineticin 2 (PK2), a cysteine-rich secreted protein, functions as an output molecule from the SCN circadian clock. PK2 messenger RNA is rhythmically expressed in the SCN, and the phase of PK2 rhythm is responsive to light ..
  49. Antoch M, Gorbacheva V, Vykhovanets O, Toshkov I, Kondratov R, Kondratova A, et al. Disruption of the circadian clock due to the Clock mutation has discrete effects on aging and carcinogenesis. Cell Cycle. 2008;7:1197-204 pubmed
    ..Here we report that mice with the functional deficiency in circadian transcription factor CLOCK (Clock/Clock mutant mice) do not display predisposition to tumor formation both during their normal lifespan or ..
  50. Asher G, Reinke H, Altmeyer M, Gutierrez Arcelus M, Hottiger M, Schibler U. Poly(ADP-ribose) polymerase 1 participates in the phase entrainment of circadian clocks to feeding. Cell. 2010;142:943-53 pubmed publisher
    ..We provide biochemical evidence that PARP-1 binds and poly(ADP-ribosyl)ates CLOCK at the beginning of the light phase...
  51. Oishi K, Ohkura N, Wakabayashi M, Shirai H, Sato K, Matsuda J, et al. CLOCK is involved in obesity-induced disordered fibrinolysis in ob/ob mice by regulating PAI-1 gene expression. J Thromb Haemost. 2006;4:1774-80 pubmed
    ..The present study investigates whether the circadian clock component CLOCK is involved in obesity-induced PAI-1 elevation...
  52. Gekakis N, Staknis D, Nguyen H, Davis F, Wilsbacher L, King D, et al. Role of the CLOCK protein in the mammalian circadian mechanism. Science. 1998;280:1564-9 pubmed
    The mouse Clock gene encodes a bHLH-PAS protein that regulates circadian rhythms and is related to transcription factors that act as heterodimers...
  53. Roybal K, Theobold D, Graham A, DiNieri J, Russo S, Krishnan V, et al. Mania-like behavior induced by disruption of CLOCK. Proc Natl Acad Sci U S A. 2007;104:6406-11 pubmed
    Circadian rhythms and the genes that make up the molecular clock have long been implicated in bipolar disorder...
  54. Sato F, Kawamoto T, Fujimoto K, Noshiro M, Honda K, Honma S, et al. Functional analysis of the basic helix-loop-helix transcription factor DEC1 in circadian regulation. Interaction with BMAL1. Eur J Biochem. 2004;271:4409-19 pubmed
    ..nucleus where it seems to play a role in regulating the mammalian circadian rhythm by suppressing the CLOCK/BMAL1-activated promoter...
  55. Turek F, Joshu C, Kohsaka A, Lin E, Ivanova G, McDearmon E, et al. Obesity and metabolic syndrome in circadian Clock mutant mice. Science. 2005;308:1043-5 pubmed
    The CLOCK transcription factor is a key component of the molecular circadian clock within pacemaker neurons of the hypothalamic suprachiasmatic nucleus...
  56. Kiyohara Y, Tagao S, Tamanini F, Morita A, Sugisawa Y, Yasuda M, et al. The BMAL1 C terminus regulates the circadian transcription feedback loop. Proc Natl Acad Sci U S A. 2006;103:10074-9 pubmed
    The circadian clock is driven by cell-autonomous transcription/translation feedback loops. The BMAL1 transcription factor is an indispensable component of the positive arm of this molecular oscillator in mammals...
  57. Oishi K, Atsumi G, Sugiyama S, Kodomari I, Kasamatsu M, Machida K, et al. Disrupted fat absorption attenuates obesity induced by a high-fat diet in Clock mutant mice. FEBS Lett. 2006;580:127-30 pubmed
    The Clock gene is a core component of the circadian clock in mammals...
  58. Yoshitane H, Ozaki H, Terajima H, Du N, Suzuki Y, Fujimori T, et al. CLOCK-controlled polyphonic regulation of circadian rhythms through canonical and noncanonical E-boxes. Mol Cell Biol. 2014;34:1776-87 pubmed publisher
    In mammalian circadian clockwork, the CLOCK-BMAL1 complex binds to DNA enhancers of target genes and drives circadian oscillation of transcription...
  59. Morse D, Cermakian N, Brancorsini S, Parvinen M, Sassone Corsi P. No circadian rhythms in testis: Period1 expression is clock independent and developmentally regulated in the mouse. Mol Endocrinol. 2003;17:141-51 pubmed
    ..We examined the expression of circadian clock genes in the testis, to assess clock control over the timing of different developmental events...
  60. Chen R, Schirmer A, Lee Y, Lee H, Kumar V, Yoo S, et al. Rhythmic PER abundance defines a critical nodal point for negative feedback within the circadian clock mechanism. Mol Cell. 2009;36:417-30 pubmed publisher
    ..loop that is driven primarily by oscillations of PER and CRY, which inhibit their own transcriptional activators, CLOCK and BMAL1. Current models posit that CRY is the dominant repressor, while PER may play an accessory role...
  61. Lin K, Kumar V, Geyfman M, Chudova D, Ihler A, Smyth P, et al. Circadian clock genes contribute to the regulation of hair follicle cycling. PLoS Genet. 2009;5:e1000573 pubmed publisher
    ..during synchronized mouse hair follicle cycling, we discovered that, in addition to circadian fluctuation, CLOCK-regulated genes are also modulated in phase with the hair growth cycle...
  62. Ramsey K, Yoshino J, Brace C, Abrassart D, Kobayashi Y, Marcheva B, et al. Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis. Science. 2009;324:651-4 pubmed publisher
    The circadian clock is encoded by a transcription-translation feedback loop that synchronizes behavior and metabolism with the light-dark cycle...
  63. Kennaway D, Owens J, Voultsios A, Boden M, Varcoe T. Metabolic homeostasis in mice with disrupted Clock gene expression in peripheral tissues. Am J Physiol Regul Integr Comp Physiol. 2007;293:R1528-37 pubmed
    The role of peripheral vs. central circadian rhythms and Clock in the maintenance of metabolic homeostasis and with aging was examined by using Clock(Delta19)+MEL mice...
  64. Maywood E, O Brien J, Hastings M. Expression of mCLOCK and other circadian clock-relevant proteins in the mouse suprachiasmatic nuclei. J Neuroendocrinol. 2003;15:329-34 pubmed
    ..It is thought to involve interlocked feedback loops in which periodic transcriptional drive to core clock genes is mediated by CLOCK/BMAL1 heterodimers...
  65. DiTacchio L, Le H, Vollmers C, Hatori M, Witcher M, Secombe J, et al. Histone lysine demethylase JARID1a activates CLOCK-BMAL1 and influences the circadian clock. Science. 2011;333:1881-5 pubmed publisher
    ..oscillators are based on a transcription-translation circuit that revolves around the transcription factors CLOCK and BMAL1...
  66. Nakashima A, Kawamoto T, Honda K, Ueshima T, Noshiro M, Iwata T, et al. DEC1 modulates the circadian phase of clock gene expression. Mol Cell Biol. 2008;28:4080-92 pubmed publisher
    DEC1 suppresses CLOCK/BMAL1-enhanced promoter activity, but its role in the circadian system of mammals remains unclear...
  67. Vitaterna M, King D, Chang A, Kornhauser J, Lowrey P, McDonald J, et al. Mutagenesis and mapping of a mouse gene, Clock, essential for circadian behavior. Science. 1994;264:719-25 pubmed
    ..rhythms in mammals, the progeny of mice treated with N-ethyl-N-nitrosourea (ENU) were screened for circadian clock mutations...
  68. Doi R, Oishi K, Ishida N. CLOCK regulates circadian rhythms of hepatic glycogen synthesis through transcriptional activation of Gys2. J Biol Chem. 2010;285:22114-21 pubmed publisher
    ..However, no direct evidence has yet implicated the circadian clock in the regulation of glycogen metabolism at the molecular level...
  69. Doi M, Hirayama J, Sassone Corsi P. Circadian regulator CLOCK is a histone acetyltransferase. Cell. 2006;125:497-508 pubmed
    ..that governs circadian rhythmicity comprises proteins whose interplay generates time-specific transcription of clock genes. The role of chromatin remodeling in a physiological setting such as the circadian clock is yet unclear...
  70. Kennaway D, Boden M, Voultsios A. Reproductive performance in female Clock Delta19 mutant mice. Reprod Fertil Dev. 2004;16:801-10 pubmed
    ..between circadian rhythmicity and rodent reproductive cyclicity is well established, but the impact of disrupted clock gene function on reproduction has not been well established...
  71. Oishi K, Shirai H, Ishida N. CLOCK is involved in the circadian transactivation of peroxisome-proliferator-activated receptor alpha (PPARalpha) in mice. Biochem J. 2005;386:575-81 pubmed
    ..that circadian expression of mouse PPARalpha mRNA requires the basic helix-loop-helix PAS (Per-Arnt-Sim) protein CLOCK, a core component of the negative-feedback loop that drives circadian oscillators in mammals...
  72. Langmesser S, Tallone T, Bordon A, Rusconi S, Albrecht U. Interaction of circadian clock proteins PER2 and CRY with BMAL1 and CLOCK. BMC Mol Biol. 2008;9:41 pubmed publisher
    Circadian oscillation of clock-controlled gene expression is mainly regulated at the transcriptional level...
  73. Oishi K, Miyazaki K, Ishida N. Functional CLOCK is not involved in the entrainment of peripheral clocks to the restricted feeding: entrainable expression of mPer2 and BMAL1 mRNAs in the heart of Clock mutant mice on Jcl:ICR background. Biochem Biophys Res Commun. 2002;298:198-202 pubmed
    ..rhythm of mPer2, BMAL1, albumin D-site binding protein (DBP), and Rev-erbalpha mRNAs in the heart of homozygous Clock mutant mice on Jcl:ICR background under the temporal feeding restriction...