Clock

Summary

Gene Symbol: Clock
Description: clock circadian regulator
Alias: circadian locomoter output cycles protein kaput, circadian locomoter output cycles kaput, rCLOCK
Species: rat
Products:     Clock

Top Publications

  1. Asher G, Gatfield D, Stratmann M, Reinke H, Dibner C, Kreppel F, et al. SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Cell. 2008;134:317-28 pubmed publisher
    ..BMAL1 and CLOCK activate the expression of Period (Per) and Cryptochrome (Cry) genes, and once PER and CRY proteins accumulate to ..
  2. Cotta Ramusino C, McDonald E, Hurov K, Sowa M, Harper J, Elledge S. A DNA damage response screen identifies RHINO, a 9-1-1 and TopBP1 interacting protein required for ATR signaling. Science. 2011;332:1313-7 pubmed publisher
    ..Three DDR candidates, the RNA processing protein INTS7, the circadian transcription factor CLOCK, and a previously uncharacterized protein RHINO, were recruited to sites of DNA damage...
  3. 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...
  4. 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...
  5. Rutter J, Reick M, Wu L, McKnight S. Regulation of clock and NPAS2 DNA binding by the redox state of NAD cofactors. Science. 2001;293:510-4 pubmed
    b>Clock:BMAL1 and NPAS2:BMAL1 are heterodimeric transcription factors that control gene expression as a function of the light-dark cycle...
  6. 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...
  7. 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...
  8. 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 ..
  9. 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 ..

More Information

Publications76

  1. Nader N, Chrousos G, Kino T. Circadian rhythm transcription factor CLOCK regulates the transcriptional activity of the glucocorticoid receptor by acetylating its hinge region lysine cluster: potential physiological implications. FASEB J. 2009;23:1572-83 pubmed publisher
    ..The basic helix-loop-helix protein CLOCK, a histone acetyltransferase (HAT), and its heterodimer partner BMAL1 are self-oscillating transcription factors ..
  2. Hogenesch J, Gu Y, Jain S, Bradfield C. The basic-helix-loop-helix-PAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors. Proc Natl Acad Sci U S A. 1998;95:5474-9 pubmed
    ..We demonstrated that MOP3 interacts with MOP4, CLOCK, hypoxia-inducible factor 1alpha (HIF1alpha), and HIF2alpha...
  3. Qi L, Boateng S. The circadian protein Clock localizes to the sarcomeric Z-disk and is a sensor of myofilament cross-bridge activity in cardiac myocytes. Biochem Biophys Res Commun. 2006;351:1054-9 pubmed
    In the mammalian heart, the circadian protein Clock regulates glucose and fatty acid metabolism. In this study, we determined some of the factors that regulate Clock expression and subcellular distribution in myocytes...
  4. Charmandari E, Chrousos G, Lambrou G, Pavlaki A, Koide H, Ng S, et al. Peripheral CLOCK regulates target-tissue glucocorticoid receptor transcriptional activity in a circadian fashion in man. PLoS ONE. 2011;6:e25612 pubmed publisher
    Circulating cortisol fluctuates diurnally under the control of the "master" circadian CLOCK, while the peripheral "slave" counterpart of the latter regulates the transcriptional activity of the glucocorticoid receptor ..
  5. Miki T, Matsumoto T, Zhao Z, Lee C. p53 regulates Period2 expression and the circadian clock. Nat Commun. 2013;4:2444 pubmed publisher
    ..This p53 response element is evolutionarily conserved and overlaps with the E-Box element critical for BMAL1/CLOCK binding and its transcriptional activation of Per2 expression...
  6. Li Y, Song X, Ma Y, Liu J, Yang D, Yan B. DNA binding, but not interaction with Bmal1, is responsible for DEC1-mediated transcription regulation of the circadian gene mPer1. Biochem J. 2004;382:895-904 pubmed
    ..Recently, both proteins were found to repress the Clock/Bmal1-activated E-box promoters (e.g. mPer1). Yeast two-hybrid assay detected interactions between Bmal1 and DECs...
  7. Richards J, Ko B, All S, Cheng K, Hoover R, Gumz M. A role for the circadian clock protein Per1 in the regulation of the NaCl co-transporter (NCC) and the with-no-lysine kinase (WNK) cascade in mouse distal convoluted tubule cells. J Biol Chem. 2014;289:11791-806 pubmed publisher
    ..Chromatin immunoprecipitation experiments demonstrated interaction of Per1 and CLOCK with the promoters of NCC, WNK1, and WNK4. This interaction was modulated by blockade of Per1 nuclear entry...
  8. Arjona A, Sarkar D. Circadian oscillations of clock genes, cytolytic factors, and cytokines in rat NK cells. J Immunol. 2005;174:7618-24 pubmed
    ..the cellular level, circadian rhythms are originated by the sustained transcriptional-translational oscillation of clock genes that form the cellular clock apparatus...
  9. Renzi A, Glaser S, Demorrow S, Mancinelli R, Meng F, Franchitto A, et al. Melatonin inhibits cholangiocyte hyperplasia in cholestatic rats by interaction with MT1 but not MT2 melatonin receptors. Am J Physiol Gastrointest Liver Physiol. 2011;301:G634-43 pubmed publisher
    ..tissues, regulates cell mitosis by interacting with melatonin receptors (MT1 and MT2) modulating cAMP and clock genes. In the liver, melatonin suppresses oxidative damage and ameliorates fibrosis...
  10. 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)...
  11. Lin R, Mo Y, Zha H, Qu Z, Xie P, Zhu Z, et al. CLOCK Acetylates ASS1 to Drive Circadian Rhythm of Ureagenesis. Mol Cell. 2017;68:198-209.e6 pubmed publisher
    ..entrainment with diurnal variation, metabolism is also tightly controlled by cell-autonomous circadian clock. Extensive studies have revealed key roles of transcription in circadian control...
  12. Annayev Y, Adar S, Chiou Y, Lieb J, Sancar A, Ye R. Gene model 129 (Gm129) encodes a novel transcriptional repressor that modulates circadian gene expression. J Biol Chem. 2014;289:5013-24 pubmed publisher
    The mammalian circadian clock is a molecular oscillator composed of a feedback loop that involves transcriptional activators CLOCK and BMAL1, and repressors Cryptochrome (CRY) and Period (PER)...
  13. Dubrovsky Y, Samsa W, Kondratov R. Deficiency of circadian protein CLOCK reduces lifespan and increases age-related cataract development in mice. Aging (Albany NY). 2010;2:936-44 pubmed
    Circadian clock is implicated in the regulation of aging. The transcription factor CLOCK, a core component of the circadian system, operates in complex with another circadian clock protein BMAL1...
  14. 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...
  15. Leclerc G, Boockfor F. Pulses of prolactin promoter activity depend on a noncanonical E-box that can bind the circadian proteins CLOCK and BMAL1. Endocrinology. 2005;146:2782-90 pubmed
    ..Sequence analysis of this fragment identified two potential E-boxes (elements known to bind CLOCK and BMAL1 circadian proteins)...
  16. Ueshima T, Kawamoto T, Honda K, Noshiro M, Fujimoto K, Nakao S, et al. Identification of a new clock-related element EL-box involved in circadian regulation by BMAL1/CLOCK and HES1. Gene. 2012;510:118-25 pubmed publisher
    Several cis-acting elements play critical roles in maintaining circadian expression of clock and clock-controlled genes...
  17. Sasaki M, Yoshitane H, Du N, Okano T, Fukada Y. Preferential inhibition of BMAL2-CLOCK activity by PER2 reemphasizes its negative role and a positive role of BMAL2 in the circadian transcription. J Biol Chem. 2009;284:25149-59 pubmed publisher
    In the molecular oscillatory mechanism governing circadian rhythms, positive regulators, including CLOCK and BMAL1, transactivate Per and Cry genes through E-box elements, and translated PER and CRY proteins negatively regulate their own ..
  18. Yang Y, Peng X, Li Y, Wang Z, Chang Quan H, Hui W, et al. The polymorphism of CLOCK gene 3111T/C C>T is associated with susceptibility of Alzheimer disease in Chinese population. J Investig Med. 2013;61:1084-7 pubmed publisher
    In the present study, it was examined whether polymorphism of circadian locomotor output cycle kaput (CLOCK) gene 3111T/C was associated with susceptibility of Alzheimer disease (AD). This study was conducted using a case-control method...
  19. Al Nuaimi Y, Hardman J, Biro T, Haslam I, Philpott M, Toth B, et al. A meeting of two chronobiological systems: circadian proteins Period1 and BMAL1 modulate the human hair cycle clock. J Invest Dermatol. 2014;134:610-619 pubmed publisher
    ..The hypothesis that the peripheral clock system is involved in hair cycle control, i.e., the anagen-to-catagen transformation, was tested...
  20. Ward S, Fernando S, Hou T, Duffield G. The transcriptional repressor ID2 can interact with the canonical clock components CLOCK and BMAL1 and mediate inhibitory effects on mPer1 expression. J Biol Chem. 2010;285:38987-9000 pubmed publisher
    ..ID2 can suppress the transactivation potential of the positive elements of the clock, CLOCK-BMAL1, on mPer1 and clock-controlled gene (CCG) activity...
  21. Chen Q, Huang C, Hu X, Li S, Zhang X. Functional CLOCK gene rs1554483 G/C polymorphism is associated with susceptibility to Alzheimer's disease in the Chinese population. J Int Med Res. 2013;41:340-6 pubmed publisher
    To examine the association between the circadian locomotor output cycles kaput (CLOCK) gene rs1554483 G/C polymorphism and susceptibility to Alzheimer's disease in Chinese people...
  22. Wang G, Du Y, Tong J. Daily oscillation and photoresponses of clock gene, Clock, and clock-associated gene, arylalkylamine N-acetyltransferase gene transcriptions in the rat pineal gland. Chronobiol Int. 2007;24:9-20 pubmed
    This study was conducted to investigate the circadian rhythms and light responses of Clock and arylalkylamine N-acetyltransferase (NAT) gene expressions in the rat pineal gland under the environmental conditions of a 12 h light (05:00-17:..
  23. Wharfe M, Mark P, Waddell B. Circadian variation in placental and hepatic clock genes in rat pregnancy. Endocrinology. 2011;152:3552-60 pubmed publisher
    b>Clock genes drive circadian rhythms in a range of physiological processes both centrally and in peripheral tissues such as the liver...
  24. Li D, Pakala S, Reddy S, Peng S, Balasenthil S, Deng C, et al. Metastasis-associated protein 1 is an integral component of the circadian molecular machinery. Nat Commun. 2013;4:2545 pubmed publisher
    The mammalian circadian clock regulates the daily cycles of many important physiological processes, but its mechanism is not well understood...
  25. Schoenhard J, Smith L, Painter C, Eren M, Johnson C, Vaughan D. Regulation of the PAI-1 promoter by circadian clock components: differential activation by BMAL1 and BMAL2. J Mol Cell Cardiol. 2003;35:473-81 pubmed
    ..Both CLOCK:BMAL1 and CLOCK:BMAL2 heterodimers activate the PAI-1 promoter through requisite proximal (-565 to -560 bp) and ..
  26. Wang G, Du Y, Tong J. [Circadian rhythms and light responses of clock gene and arylalkylamine N-acetyltransferase gene expressions in the pineal gland of rats]. Sheng Li Xue Bao. 2005;57:97-102 pubmed
    This study was to investigate the circadian rhythms and light responses of Clock gene and arylalkylamine N-acetyltransferase (NAT) gene expressions in the rat pineal gland under the 12 h-light : 12 h-dark cycle condition (LD) and ..
  27. Malatesta M, Baldelli B, Battistelli S, Fattoretti P, Bertoni Freddari C. Aging affects the distribution of the circadian CLOCK protein in rat hepatocytes. Microsc Res Tech. 2005;68:45-50 pubmed
    ..b>CLOCK protein is a transcription factor essential for normal circadian rhythms and recent studies have demonstrated that ..
  28. Li Y, Jin M, Sun B, Feng X. [Changes of biological clock protein in neonatal rats with hypoxic-ischemic brain damage]. Zhongguo Dang Dai Er Ke Za Zhi. 2013;15:62-6 pubmed
    To study the effects of biological clock protein on circadian disorders in hypoxic-ischemic brain damage (HIBD) by examining levels of CLOCK and BMAL1 proteins in the pineal gland of neonatal rats...
  29. Han D, Lee Y, Kim K, Kim C, Cho S. Modulation of glucocorticoid receptor induction properties by core circadian clock proteins. Mol Cell Endocrinol. 2014;383:170-80 pubmed publisher
    ..Here, we demonstrate that CLOCK/BMAL1, the core circadian clock components, reduces maximal GR transactivation (A(max)) as well as efficacy (EC??) ..
  30. 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...
  31. 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...
  32. Shieh K, Yang S, Lu X, Akil H, Watson S. Diurnal rhythmic expression of the rhythm-related genes, rPeriod1, rPeriod2, and rClock, in the rat brain. J Biomed Sci. 2005;12:209-17 pubmed
    High densities of the mRNA of three rhythm-related genes, rPeriod1 (rPer1), rPer2, and rClock, which share high homology in Drosophila and mammals, are found in the rat hypothalamic suprachiasmatic nucleus (SCN)...
  33. Jiang W, Li S, Liu J, Sun Y, Zhou S, Zhu W, et al. Hippocampal CLOCK protein participates in the persistence of depressive-like behavior induced by chronic unpredictable stress. Psychopharmacology (Berl). 2013;227:79-92 pubmed publisher
    Circadian disturbances are strongly linked with major depression. The circadian proteins CLOCK and BMAL1 are abundantly expressed but function differently in the suprachiasmatic nucleus (SCN) and hippocampus...
  34. Chen H, Huang C, You C, Wang Z, Si Qing H. Polymorphism of CLOCK gene rs 4580704 C > G is associated with susceptibility of Alzheimer's disease in a Chinese population. Arch Med Res. 2013;44:203-7 pubmed publisher
    The association of polymorphism of circadian locomotor output cycle kaput (CLOCK) gene rs 4580704 C/G with susceptibility of Alzheimer's disease (AD) was examined in the present study...
  35. Duffield G, Watson N, Mantani A, Peirson S, Robles Murguia M, Loros J, et al. A role for Id2 in regulating photic entrainment of the mammalian circadian system. Curr Biol. 2009;19:297-304 pubmed publisher
    ..promoter reporter revealed the potential for ID1, ID2, and ID3 proteins to interact with the canonical basic HLH clock proteins BMAL1 and CLOCK...
  36. Kawamoto T, Noshiro M, Sato F, Maemura K, Takeda N, Nagai R, et al. A novel autofeedback loop of Dec1 transcription involved in circadian rhythm regulation. Biochem Biophys Res Commun. 2004;313:117-24 pubmed
    An autofeedback loop associated with transcription of clock gene(s), Per(s), is generally accepted as the molecular machinery of circadian rhythm generation, in which CLOCK/BMAL act as positive regulators and PER/CRY as negative ones...
  37. Goriki A, Hatanaka F, Myung J, Kim J, Yoritaka T, Tanoue S, et al. A novel protein, CHRONO, functions as a core component of the mammalian circadian clock. PLoS Biol. 2014;12:e1001839 pubmed publisher
    Circadian rhythms are controlled by a system of negative and positive genetic feedback loops composed of clock genes...
  38. 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...
  39. Kwak Y, Lundkvist G, Brask J, Davidson A, Menaker M, Kristensson K, et al. Interferon-gamma alters electrical activity and clock gene expression in suprachiasmatic nucleus neurons. J Biol Rhythms. 2008;23:150-9 pubmed publisher
    ..They analyzed the effect of the treatment on the spontaneous spiking pattern and rhythmic expression of the "clock gene," Period 1...
  40. Baeza Raja B, Eckel Mahan K, Zhang L, Vagena E, Tsigelny I, Sassone Corsi P, et al. p75 neurotrophin receptor is a clock gene that regulates oscillatory components of circadian and metabolic networks. J Neurosci. 2013;33:10221-34 pubmed publisher
    ..Here we show that p75(NTR) is an oscillating gene regulated by the helix-loop-helix transcription factors CLOCK and BMAL1. The p75(NTR) promoter contains evolutionarily conserved noncanonical E-box enhancers...
  41. Muhlbauer E, Wolgast S, Finckh U, Peschke D, Peschke E. Indication of circadian oscillations in the rat pancreas. FEBS Lett. 2004;564:91-6 pubmed
    ..reverse transcription-polymerase chain reaction (RT-PCR) was used in analysis of the expression of the major clock genes Per1, Per2, Bmal1, Cry1, Tim (timeless) and Clock, as well as of the output genes Dbp and Rev-erbalpha in ..
  42. Poletini M, Kennett J, McKee D, Freeman M. Central clock regulates the cervically stimulated prolactin surges by modulation of dopamine and vasoactive intestinal polypeptide release in ovariectomized rats. Neuroendocrinology. 2010;91:179-88 pubmed publisher
    ..The suprachiasmatic nucleus (SCN) controls this rhythm, and we propose that it does so through clock gene expression within the SCN...
  43. Matagne V, Kim J, Ryu B, Hur M, Kim M, Kim K, et al. Thyroid transcription factor 1, a homeodomain containing transcription factor, contributes to regulating periodic oscillations in GnRH gene expression. J Neuroendocrinol. 2012;24:916-29 pubmed publisher
    ..Rat GnRH neurones in situ contain key proteins components of the positive (BMAL1, CLOCK) and negative (PER1) limbs of the circadian oscillator, and these proteins repress Ttf1 promoter activity in vitro...
  44. Namihira M, Honma S, Abe H, Tanahashi Y, Ikeda M, Honma K. Circadian rhythms and light responsiveness of mammalian clock gene, Clock and BMAL1, transcripts in the rat retina. Neurosci Lett. 1999;271:1-4 pubmed
    Circadian expression and light-responsiveness of the mammalian clock genes, Clock and BMAL1, in the rat retina were examined by in situ hydbribization under constant darkness...
  45. Zeman M, Szántóová K, Stebelova K, Mravec B, Herichova I. Effect of rhythmic melatonin administration on clock gene expression in the suprachiasmatic nucleus and the heart of hypertensive TGR(mRen2)27 rats. J Hypertens Suppl. 2009;27:S21-6 pubmed publisher
    ..The effect of melatonin on blood pressure was monitored, and the expression of clock genes per2 and bmal1 and melatonin receptor MT1 in the suprachiasmatic nucleus (SCN) and the heart was measured by ..
  46. Miyazaki M, Schroder E, Edelmann S, Hughes M, Kornacker K, Balke C, et al. Age-associated disruption of molecular clock expression in skeletal muscle of the spontaneously hypertensive rat. PLoS ONE. 2011;6:e27168 pubmed publisher
    ..Woon et al. (2007) linked the circadian clock gene Bmal1 to hypertension and metabolic dysfunction in the SHR...
  47. Nakagami K, Uchida T, Ohwada S, Koibuchi Y, Suda Y, Sekine T, et al. Increased choline kinase activity and elevated phosphocholine levels in human colon cancer. Jpn J Cancer Res. 1999;90:419-24 pubmed
    ..This study suggests that choline kinase might play a role in growth promotion or signal transduction in carcinogenesis. ..
  48. Xu C, Krager S, Liao D, Tischkau S. Disruption of CLOCK-BMAL1 transcriptional activity is responsible for aryl hydrocarbon receptor-mediated regulation of Period1 gene. Toxicol Sci. 2010;115:98-108 pubmed publisher
    ..nuclear transporter-simple minded domain transcription factor that shares structural similarity with circadian clock genes and readily interacts with components of the molecular clock...
  49. Spengler M, Kuropatwinski K, Comas M, Gasparian A, Fedtsova N, Gleiberman A, et al. Core circadian protein CLOCK is a positive regulator of NF-?B-mediated transcription. Proc Natl Acad Sci U S A. 2012;109:E2457-65 pubmed publisher
    The circadian clock controls many physiological parameters including immune response to infectious agents, which is mediated by activation of the transcription factor NF-?B...
  50. Devos J, Weselake S, Wevrick R. Magel2, a Prader-Willi syndrome candidate gene, modulates the activities of circadian rhythm proteins in cultured cells. J Circadian Rhythms. 2011;9:12 pubmed publisher
    ..nucleus of the hypothalamus, where its expression cycles in a circadian pattern comparable to that of clock-controlled genes...
  51. Li M, Ruan H, Hughes M, Lee J, Singh J, Jones S, et al. O-GlcNAc signaling entrains the circadian clock by inhibiting BMAL1/CLOCK ubiquitination. Cell Metab. 2013;17:303-10 pubmed publisher
    ..Here we show that the hexosamine/O-GlcNAc pathway modulates peripheral clock oscillation...
  52. 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...
  53. Peruquetti R, de Mateo S, Sassone Corsi P. Circadian proteins CLOCK and BMAL1 in the chromatoid body, a RNA processing granule of male germ cells. PLoS ONE. 2012;7:e42695 pubmed publisher
    ..Targeted ablation of the Bmal1 and Clock genes, which encode central regulators of the circadian clock also result in fertility defects caused by problems ..
  54. Bellet M, Zocchi L, Sassone Corsi P. The RelB subunit of NF?B acts as a negative regulator of circadian gene expression. Cell Cycle. 2012;11:3304-11 pubmed publisher
    ..The molecular organization of the circadian clock is complex, involving various elements organized in feedback regulatory loops...
  55. 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 ..
  56. Hamaguchi H, Fujimoto K, Kawamoto T, Noshiro M, Maemura K, Takeda N, et al. Expression of the gene for Dec2, a basic helix-loop-helix transcription factor, is regulated by a molecular clock system. Biochem J. 2004;382:43-50 pubmed
    ..oscillation in the suprachiasmatic nucleus, and Dec2 inhibits transcription from the Per1 promoter induced by Clock/Bmal1 [Honma, Kawamoto, Takagi, Fujimoto, Sato, Noshiro, Kato and Honma (2002) Nature (London) 419, 841-844]...
  57. Woon P, Curtis A, Kaisaki P, Argoud K, Wallace K, Bihoreau M, et al. Genomic organization of the rat Clock gene and sequence analysis in inbred rat strains. Genomics. 2006;87:208-17 pubmed
    While mutations in genes that function in the core molecular clock may disrupt circadian periodicity, their relevance to diurnal variation in metabolic, cardiovascular, and respiratory function is unknown...
  58. Abe H, Honma S, Namihira M, Tanahashi Y, Ikeda M, Yu W, et al. Phase-dependent induction by light of rat Clock gene expression in the suprachiasmatic nucleus. Brain Res Mol Brain Res. 1999;66:104-10 pubmed
    To clarify the role of Clock in the photic signal transduction of rat circadian clock, we cloned and sequenced rat Clock and examined the effect of a single light pulse on the Clock mRNA expression in the suprachiasmatic nucleus (SCN) by ..
  59. Soltésová D, Monosíková J, Koyšová L, Vesela A, Mravec B, Herichova I. Effect of streptozotocin-induced diabetes on clock gene expression in tissues inside and outside the blood-brain barrier in rat. Exp Clin Endocrinol Diabetes. 2013;121:466-74 pubmed publisher
    ..The molecular mechanism of circadian oscillations is based on the rhythmic expression of clock genes organized in feedback loops...
  60. 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...
  61. 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...
  62. Kovacikova Z, Sladek M, Bendova Z, Illnerova H, Sumova A. Expression of clock and clock-driven genes in the rat suprachiasmatic nucleus during late fetal and early postnatal development. J Biol Rhythms. 2006;21:140-8 pubmed
    The SCN as a site of the circadian clock itself exhibits rhythmicity. A molecular clockwork responsible for the rhythmicity consists of clock genes and their negative and positive transcriptional-translational feedback loops...
  63. Lande Diner L, Boyault C, Kim J, Weitz C. A positive feedback loop links circadian clock factor CLOCK-BMAL1 to the basic transcriptional machinery. Proc Natl Acad Sci U S A. 2013;110:16021-6 pubmed publisher
    ..a negative feedback loop in which the heterodimeric transcription factor circadian locomotor output cycles kaput (CLOCK)-brain, muscle Arnt-like 1 (BMAL1) drives the expression of its own inhibitors, the PERIOD and CRYPTOCHROME ..
  64. Kerman I, Clinton S, Simpson D, Bedrosian T, Bernard R, Akil H, et al. Inborn differences in environmental reactivity predict divergent diurnal behavioral, endocrine, and gene expression rhythms. Psychoneuroendocrinology. 2012;37:256-69 pubmed publisher
    Circadian dysfunction has long been implicated in the etiology of mood disorders. The gene Clock and related molecules (e.g...
  65. Koyanagi S, Hamdan A, Horiguchi M, Kusunose N, Okamoto A, Matsunaga N, et al. cAMP-response element (CRE)-mediated transcription by activating transcription factor-4 (ATF4) is essential for circadian expression of the Period2 gene. J Biol Chem. 2011;286:32416-23 pubmed publisher
    ..oscillates in a circadian manner, which in turn also sustains core oscillation machinery of the circadian clock. Here, we show that among the ATF/CREB family proteins, ATF4 is essential for the circadian expression of the ..
  66. Han X, Ding X, Xu L, Liu M, Feng X. [Expression profiles of miRNA-182 and Clock mRNA in the pineal gland of neonatal rats with hypoxic-ischemic brain damage]. Zhongguo Dang Dai Er Ke Za Zhi. 2016;18:270-6 pubmed
    ..RT-PCR analysis was performed to measure the expression profiles of the chosen miRNA and the targeted gene Clock mRNA in the pineal gland at 0, 24, 48 and 72 hours after HIBD...
  67. Sellix M, Egli M, Poletini M, McKee D, Bosworth M, Fitch C, et al. Anatomical and functional characterization of clock gene expression in neuroendocrine dopaminergic neurons. Am J Physiol Regul Integr Comp Physiol. 2006;290:R1309-23 pubmed
    ..activity in suprachiasmatic nucleus (SCN) neurons result from autoregulatory feedback loops of circadian clock gene transcription factors...