The mammalian clock component PERIOD2 coordinates circadian output by interaction with nuclear receptors
Open accessAbstract
Mammalian circadian clocks provide a temporal framework to synchronize biological functions. To obtain robust rhythms with a periodicity of about a day, these clocks use molecular oscillators consisting of two interlocked feedback loops. The core loop generates rhythms by transcriptional repression via the Period (PER) and Cryptochrome (CRY) proteins, whereas the stabilizing loop establishes roughly antiphasic rhythms via nuclear receptors. Nuclear receptors also govern many pathways that affect metabolism and physiology. Here we show that the core loop component PER2 can coordinate circadian output with the circadian oscillator. PER2 interacts with nuclear receptors including PPARalpha and REV-ERBalpha and serves as a coregulator of nuclear receptor-mediated transcription. Consequently, PER2 is rhythmically bound at the promoters of nuclear receptor target genes in vivo. In this way, the circadian oscillator can modulate the expression of nuclear receptor target genes like Bmal1, Hnf1alpha, and Glucose-6-phosphatase. The concept that PER2 may propagate clock information to metabolic pathways via nuclear receptors adds an important facet to the clock-dependent regulation of biological networks.
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Per2 mutant mice show reduced fasting glycemia, loss of rhythmic glycogen accumulation in the liver, elevated plasma insulin levels and impaired gluconeogenesis.
“Per2 mutant mice show reduced fasting glycemia, a loss of rhythmic glycogen accumulation in the liver, elevated plasma insulin levels and impaired gluconeogenesis [20–22]”
From Circadian control of glucose metabolism (2014) · cites this paper as [20]
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Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
LAEMMLI, U. K. (1970) · Nature · doi:10.1038/227680a0 · Cited by 249,961 · see citing works
Coordinated Transcription of Key Pathways in the Mouse by the Circadian Clock
Panda, S., Antoch, M. P., Miller, B. H., Su, A. I., Schook, A. C., Straume, M., Schultz, P. G., Kay, S. A., Takahashi, J. S., & Hogenesch, J. B. (2002) · Cell · doi:10.1016/s0092-8674(02)00722-5 · Cited by 2,272 · see citing works
Preitner, N., Damiola, F., Luis-Lopez-Molina, Zakany, J., Duboule, D., Albrecht, U., & Schibler, U. (2002) · Cell · doi:10.1016/s0092-8674(02)00825-5 · Cited by 2,198 · see citing works
A signature motif in transcriptional co-activators mediates binding to nuclear receptors
Heery, D. M., Kalkhoven, E., Hoare, S., & Parker, M. G. (1997) · Nature · doi:10.1038/42750 · Cited by 2,128 · see citing works
Role of the CLOCK Protein in the Mammalian Circadian Mechanism
Gekakis, N., Staknis, D., Nguyen, H. B., Davis, F. C., Wilsbacher, L. D., King, D. P., Takahashi, J. S., & Weitz, C. J. (1998) · Science · doi:10.1126/science.280.5369.1564 · Cited by 1,997 · see citing works
Resetting of circadian time in peripheral tissues by glucocorticoid signaling
Balsalobre, A., Brown, S. A., Marcacci, L., Tronche, F., Kellendonk, C., Reichardt, H. M., Schütz, G., & Schibler, U. (2000) · Science · doi:10.1126/science.289.5488.2344 · Cited by 1,859 · see citing works
Mop3 is an essential component of the master circadian pacemaker in mammals.
Bunger, M. K., Wilsbacher, L. D., Moran, S. M., Clendenin, C., Radcliffe, L. A., Hogenesch, J. B., Simon, M. C., Takahashi, J. S., & Bradfield, C. A. (2000) · Cell · doi:10.1016/s0092-8674(00)00205-1 · Cited by 1,621 · see citing works
mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop
Kume, K., Zylka, M. J., Sriram, S., Shearman, L. P., Weaver, D. R., Jin, X., Maywood, E. S., Hastings, M. H., & Reppert, S. M. (1999) · Cell · doi:10.1016/s0092-8674(00)81014-4 · Cited by 1,617 · see citing works
Mutations in the hepatocyte nuclear factor-1α gene in maturity-onset diabetes of the young (MODY3)
Yamagata, K., Oda, N., Kaisaki, P. J., Menzel, S., Furuta, H., Vaxillaire, M., Southam, L., Cox, R., Lathrop, M. G., Boriraj, V. V., et al. (1996) · Nature · doi:10.1038/384455a0 · Cited by 1,610 · see citing works
Extensive and divergent circadian gene expression in liver and heart
Storch, K.-F., Lipan, O., Leykin, I., Viswanathan, N., Davis, F. C., Wong, W. H., & Weitz, C. J. (2002) · Nature · doi:10.1038/nature744 · Cited by 1,509 · see citing works
Positional Cloning of the Mouse Circadian Gene
King, D. P., Zhao, Y., Sangoram, A. M., Wilsbacher, L. D., Tanaka, M., Antoch, M. P., Steeves, T. D. L., Vitaterna, M. H., Kornhauser, J. M., Lowrey, P. L., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80245-7 · Cited by 1,382 · see citing works
SIRT1 regulates circadian clock gene expression through PER2 deacetylation
Asher, G., Gatfield, D., Stratmann, M., Reinke, H., Dibner, C., Kreppel, F., Mostoslavsky, R., Alt, F. W., & Schibler, U. (2008) · Cell · doi:10.1016/j.cell.2008.06.050 · Cited by 1,376 · see citing works
Interacting molecular loops in the mammalian circadian clock
Shearman, L. P., Sriram, S., Weaver, D. R., Maywood, E. S., Chaves, I., Zheng, B., Kume, K., Lee, C. C., van der, G. T. J., Horst, et al. (2000) · Science · doi:10.1126/science.288.5468.1013 · Cited by 1,367 · see citing works
Posttranslational Mechanisms Regulate the Mammalian Circadian Clock
Lee, C., Etchegaray, J., Cagampang, F. R. A., Loudon, A. S. I., & Reppert, S. M. (2001) · Cell · doi:10.1016/s0092-8674(01)00610-9 · Cited by 1,158 · see citing works
Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels
Hardin, P. E., Hall, J. C., & Rosbash, M. (1990) · Nature · doi:10.1038/343536a0 · Cited by 1,156 · see citing works
A Functional Genomics Strategy Reveals Rora as a Component of the Mammalian Circadian Clock
Sato, T. K., Panda, S., Miraglia, L. J., Reyes, T. M., Rudic, R. D., McNamara, P., Naik, K. A., FitzGerald, G. A., Kay, S. A., & Hogenesch, J. B. (2004) · Neuron · doi:10.1016/j.neuron.2004.07.018 · Cited by 1,115 · see citing works
Rudic, R. D., McNamara, P., Curtis, A.-M., Boston, R. C., Panda, S., Hogenesch, J. B., & FitzGerald, G. A. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020377 · Cited by 1,059 · see citing works
Physiological significance of a peripheral tissue circadian clock
Lamia, K. A., Storch, K.-F., & Weitz, C. J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806717105 · Cited by 1,048 · see citing works
Circadian Gene Expression in Individual Fibroblasts
Nagoshi, E., Saini, C., Bauer, C. R., Laroche, T., Naef, F., & Schibler, U. (2004) · Cell · doi:10.1016/j.cell.2004.11.015 · Cited by 1,003 · see citing works
Mutations in the hepatocyte nuclear factor-4α gene in maturity-onset diabetes of the young (MODY1)
Yamagata, K., Furuta, H., Oda, N., Kaisaki, P. J., Menzel, S., Cox, N. J., Fajans, S. S., Signorini, S. G., Stoffel, M., & Bell, G. I. (1996) · Nature · doi:10.1038/384458a0 · Cited by 975 · see citing works
Nuclear Receptor Expression Links the Circadian Clock to Metabolism
Yang, X., Downes, M., Yu, R. T., Bookout, A. L., He, W., Straume, M., Mangelsdorf, D. J., & Evans, R. M. (2006) · Cell · doi:10.1016/j.cell.2006.06.050 · Cited by 934 · see citing works
Nonredundant roles of the mPer1 and mPer2 genes in the mammalian circadian clock.
Zheng, B., Albrecht, U., Kaasik, K., Sage, M., Lu, W., Vaishnav, S., Li, Q., Sun, Z. S., Eichele, G., Bradley, A., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00380-4 · Cited by 900 · see citing works
Self-citationDifferential Functions of mPer1, mPer2, and mPer3 in the SCN Circadian Clock
Bae, K., Jin, X., Maywood, E. S., Hastings, M. H., Reppert, S. M., & Weaver, D. R. (2001) · Neuron · doi:10.1016/s0896-6273(01)00302-6 · Cited by 900 · see citing works
A Molecular Mechanism Regulating Rhythmic Output from the Suprachiasmatic Circadian Clock
Jin, X., Shearman, L. P., Weaver, D. R., Zylka, M. J., Vries, G. J. D., & Reppert, S. M. (1999) · Cell · doi:10.1016/s0092-8674(00)80959-9 · Cited by 891 · see citing works
A Differential Response of Two Putative Mammalian Circadian Regulators, mper1and mper2, to Light
Albrecht, U., Sun, Z. S., Eichele, G., & Lee, C. C. (1997) · Cell · doi:10.1016/s0092-8674(00)80495-x · Cited by 879 · see citing works
Self-citationA transcription factor response element for gene expression during circadian night
Ueda, H. R., Chen, W., Adachi, A. A., Wakamatsu, H., Hayashi, S., Takasugi, T., Nagano, M., Nakahama, K., Suzuki, Y., Sugano, S., et al. (2002) · Nature · doi:10.1038/nature00906 · Cited by 850 · see citing works
Circadian oscillation of a mammalian homologue of the Drosophila period gene
Tei, H., Okamura, H., Shigeyoshi, Y., Fukuhara, C., Ozawa, R., Hirose, M., & Sakaki, Y. (1997) · Nature · doi:10.1038/39086 · Cited by 792 · see citing works
System-level identification of transcriptional circuits underlying mammalian circadian clocks
Ueda, H. R., Hayashi, S., Chen, W., Sano, M., Machida, M., Shigeyoshi, Y., Iino, M., & Hashimoto, S. (2005) · Nature Genetics · doi:10.1038/ng1504 · Cited by 786 · see citing works
Two period Homologs: Circadian Expression and Photic Regulation in the Suprachiasmatic Nuclei
Shearman, L. P., Zylka, M. J., Weaver, D. R., Kolakowski, L. F., & Reppert, S. M. (1997) · Neuron · doi:10.1016/s0896-6273(00)80417-1 · Cited by 781 · see citing works
Hogenesch, J. B., Gu, Y.-Z., Jain, S. R., & Bradfield, C. A. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.10.5474 · Cited by 781 · see citing works
The mPer2 gene encodes a functional component of the mammalian circadian clock
Zheng, B., Larkin, D. W., Albrecht, U., Sun, Z. S., Sage, M., Eichele, G., Lee, C. C., & Bradley, A. (1999) · Nature · doi:10.1038/22118 · Cited by 718 · see citing works
Rev-erbα, a Heme Sensor That Coordinates Metabolic and Circadian Pathways
Yin, L., Wu, N., Curtin, J. C., Qatanani, M., Szwergold, N. R., Reid, R. A., Waitt, G. M., Parks, D. J., Pearce, K. H., Wisely, G. B., et al. (2007) · Science · doi:10.1126/science.1150179 · Cited by 707 · see citing works
RIGUI, a putative mammalian ortholog of the Drosophila period gene.
Sun, Z. S., Albrecht, U., Zhuchenko, O., Bailey, J., Eichele, G., & Lee, C.-C. (1997) · Cell · doi:10.1016/s0092-8674(00)80366-9 · Cited by 706 · see citing works
Light-Independent Role of CRY1 and CRY2 in the Mammalian Circadian Clock
Griffin, E. A., Staknis, D., & Weitz, C. J. (1999) · Science · doi:10.1126/science.286.5440.768 · Cited by 646 · see citing works
The CoRNR motif controls the recruitment of corepressors by nuclear hormone receptors
Hu, X., & Lazar, M. A. (1999) · Nature · doi:10.1038/47069 · Cited by 642 · see citing works
Ripperger, J. A., & Schibler, U. (2006) · Nature Genetics · doi:10.1038/ng1738 · Cited by 593 · see citing works
NPAS2: an analog of clock operative in the mammalian forebrain
Reick, M., Garcia, J. A., Dudley, C., & McKnight, S. L. (2001) · Science · doi:10.1126/science.1060699 · Cited by 572 · see citing works
Identification of heme as the ligand for the orphan nuclear receptors REV-ERBα and REV-ERBβ
Raghuram, S., Stayrook, K. R., Huang, P., Rogers, P. M., Nosie, A. K., McClure, D. B., Burris, L. L., Khorasanizadeh, S., Burris, T. P., & Rastinejad, F. (2007) · Nature Structural & Molecular Biology · doi:10.1038/nsmb1344 · Cited by 560 · see citing works
CLOCK and NPAS2 have overlapping roles in the suprachiasmatic circadian clock
DeBruyne, J. P., Weaver, D. R., & Reppert, S. M. (2007) · Nature Neuroscience · doi:10.1038/nn1884 · Cited by 484 · see citing works
REV-ERBα Participates in Circadian SREBP Signaling and Bile Acid Homeostasis
Martelot, G. L., Claudel, T., Gatfield, D., Schaad, O., Kornmann, B., Sasso, G. L., Moschetta, A., & Schibler, U. (2009) · PLoS Biology · doi:10.1371/journal.pbio.1000181 · Cited by 448 · see citing works
Ripperger, J. A., Shearman, L. P., Reppert, S. M., & Schibler, U. (2000) · Genes & Development · doi:10.1101/gad.14.6.679 · Cited by 429 · see citing works
Regulation of Monoamine Oxidase A by Circadian-Clock Components Implies Clock Influence on Mood
Hampp, G., Ripperger, J. A., Houben, T., Schmutz, I., Blex, C., Perreau‐Lenz, S., Brunk, I., Spanagel, R., Ahnert‐Hilger, G., Meijer, J. H., et al. (2008) · Current Biology · doi:10.1016/j.cub.2008.04.012 · Cited by 419 · see citing works
Liu, A. C., Tran, H. G., Zhang, E. E., Priest, A. A., Welsh, D. K., & Kay, S. A. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000023 · Cited by 396 · see citing works
Canaple, L., Rambaud, J., Dkhissi‐Benyahya, O., Rayet, B., Tan, N. S., Michalik, L., Delaunay, F., Wahli, W., & Laudet, V. (2006) · Molecular Endocrinology · doi:10.1210/me.2006-0052 · Cited by 353 · see citing works
Lavery, D. J., & Schibler, U. (1993) · Genes & Development · doi:10.1101/gad.7.10.1871 · Cited by 300 · see citing works
Yin, L., & Lazar, M. A. (2005) · Molecular Endocrinology · doi:10.1210/me.2005-0057 · Cited by 274 · see citing works
The coactivator LXXLL nuclear receptor recognition motif
Savkur, R. S., & Burris, T. P. (2004) · Journal of Peptide Research · doi:10.1111/j.1399-3011.2004.00126.x · Cited by 263 · see citing works
Cermakian, N., Monaco, L., Pando, M. P., Dierich, A., & Sassone‐Corsi, P. (2001) · The EMBO Journal · doi:10.1093/emboj/20.15.3967 · Cited by 252 · see citing works
Jud, C., Schmutz, I., Hampp, G., Oster, H., & Albrecht, U. (2005) · Biological Procedures Online · doi:10.1251/bpo109 · Cited by 235 · see citing works
Harding, H. P., & Lazar, M. A. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.9.4791 · Cited by 210 · see citing works
The Orphan Receptor Rev-ErbAα Activates Transcription via a Novel Response element
Harding, H. P., & Lazar, M. A. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.5.3113-3121.1993 · Cited by 208 · see citing works
Tian, J. M., & Schibler, U. (1991) · Genes & Development · doi:10.1101/gad.5.12a.2225 · Cited by 186 · see citing works
Mammalian circadian signaling networks and therapeutic targets
Liu, A. C., Lewis, W. G., & Kay, S. A. (2007) · Nature Chemical Biology · doi:10.1038/nchembio.2007.37 · Cited by 177 · see citing works
Peripheral circadian oscillators require CLOCK
DeBruyne, J. P., Weaver, D. R., & Reppert, S. M. (2007) · Current Biology · doi:10.1016/j.cub.2007.05.067 · Cited by 160 · see citing works
Interaction of circadian clock proteins PER2 and CRY with BMAL1 and CLOCK
Langmesser, S., Tallone, T., Bordon, A., Rusconi, S., & Albrecht, U. (2008) · BMC Molecular Biology · doi:10.1186/1471-2199-9-41 · Cited by 131 · see citing works
Disruption of mCry2 restores circadian rhythmicity in mPer2 mutant micePreprint
Oster, H., Yasui, A., van der Horst, G. T. J., & Albrecht, U. (2002) · Genes & Development · doi:10.1101/gad.233702 · Cited by 116 · see citing works
Petrescu, I., Bojan, O., Saied, M., Bârzu, O., Schmidt, F. H., & Kühnle, H. F. (1979) · Analytical Biochemistry · doi:10.1016/0003-2697(79)90582-7 · Cited by 113 · see citing works
Hennig, S., Strauss, H. M., Vanselow, K., Yıldız, Ö., Schulze, S., Arens, J., Kramer, A., & Wolf, E. (2009) · PLoS Biology · doi:10.1371/journal.pbio.1000094 · Cited by 97 · see citing works
Loss of circadian rhythmicity in agingmPer1-/-mCry2-/-mutant micePreprint
Oster, H., Baeriswyl, S., van der Horst, G. T. J., & Albrecht, U. (2003) · Genes & Development · doi:10.1101/gad.256103 · Cited by 89 · see citing works
Nordlie, R. C., & Jorgenson, R. A. (1976) · Springer eBooks · doi:10.1007/978-1-4684-2655-7_13 · Cited by 86 · see citing works
Downes, M., Burke, L. J., Bailey, P. J., & Muscat, G. E. O. (1996) · Nucleic Acids Research · doi:10.1093/nar/24.22.4379 · Cited by 81 · see citing works
The Multiple Facets of Per2Preprint
Albrecht, U., Bordon, A., Schmutz, I., & Ripperger, J. A. (2007) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2007.72.001 · Cited by 77 · see citing works
Structural Insight into the Constitutive Repression Function of the Nuclear Receptor Rev-erbβ
Woo, E., Jeong, D. G., Lim, M.-Y., Kim, S. J., Kim, K.-J., Yoon, S., Park, B.-C., & Ryu, S. E. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.08.037 · Cited by 54 · see citing works
Jones, O. T. G., & Wood, J. D. (1996) · Methods · doi:10.1006/meth.1996.0068 · Cited by 13 · see citing works
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Central and Peripheral Circadian Clocks in Mammals
Mohawk, J. A., Green, C. B., & Takahashi, J. S. (2012) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-060909-153128 · Cited by 2,265 · see citing works
Circadian integration of metabolism and energetics
Bass, J., & Takahashi, J. S. (2010) · Science · doi:10.1126/science.1195027 · Cited by 1,910 · see citing works
Transcriptional architecture and chromatin landscape of the core circadian clock in mammals
Koike, N., Yoo, S.-H., Huang, H.-C., Kumar, V., Lee, C., Kim, T.-K., & Takahashi, J. S. (2012) · Science · doi:10.1126/science.1226339 · Cited by 1,464 · see citing works
Molecular architecture of the mammalian circadian clock
Partch, C. L., Green, C. B., & Takahashi, J. S. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2013.07.002 · Cited by 1,449 · see citing works
Timing to perfection: the biology of central and peripheral circadian clocks
Albrecht, U. (2012) · Neuron · doi:10.1016/j.neuron.2012.04.006 · Cited by 915 · see citing works
Circadian topology of metabolism
Bass, J. T. (2012) · Nature · doi:10.1038/nature11704 · Cited by 610 · see citing works
Crosstalk between components of circadian and metabolic cycles in mammals
Asher, G., & Schibler, U. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.01.006 · Cited by 601 · see citing works
Crosstalk between metabolism and circadian clocks
Reinke, H., & Asher, G. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0096-9 · Cited by 598 · see citing works
Cryptochromes mediate rhythmic repression of the glucocorticoid receptor
Lamia, K. A., Papp, S. J., Yu, R. T., Barish, G. D., Uhlenhaut, N. H., Jonker, J. W., Downes, M., & Evans, R. M. (2011) · Nature · doi:10.1038/nature10700 · Cited by 590 · see citing works
REV-ERB and ROR nuclear receptors as drug targets
Kojetin, D. J., & Burris, T. P. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4100 · Cited by 580 · see citing works
Metabolism and the Circadian Clock Converge
Eckel‐Mahan, K. L., & Sassone‐Corsi, P. (2013) · Physiological Reviews · doi:10.1152/physrev.00016.2012 · Cited by 530 · see citing works
PER2 controls lipid metabolism by direct regulation of PPARγ
Grimaldi, B., Bellet, M. M., Katada, S., Astarita, G., Hirayama, J., Amin, R. H., Granneman, J. G., Piomelli, D., Leff, T., & Sassone-Corsi, P. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.10.005 · Cited by 489 · see citing works
Rey, G., Cesbron, F., Rougemont, J., Reinke, H., Brunner, M., & Naef, F. (2011) · PLoS Biology · doi:10.1371/journal.pbio.1000595 · Cited by 473 · see citing works
The circadian regulation of food intake
Challet, E. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0210-x · Cited by 428 · see citing works
Sleep and Circadian Rhythm Regulation in Early Parkinson Disease
Breen, D. P., Vuono, R., Nawarathna, U., Fisher, K., Shneerson, J. M., Reddy, A. B., & Barker, R. A. (2014) · JAMA Neurology · doi:10.1001/jamaneurol.2014.65 · Cited by 440 · see citing works
Circadian Control of DRP1 Activity Regulates Mitochondrial Dynamics and Bioenergetics
Schmitt, K., Grimm, A., Dallmann, R., Oettinghaus, B., Restelli, L. M., Witzig, M., Ishihara, N., Mihara, K., Ripperger, J. A., Albrecht, U., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.01.011 · Cited by 336 · see citing works
Circadian control of glucose metabolism
Kalsbeek, A., la Fleur, S., & Fliers, E. (2014) · Molecular Metabolism · doi:10.1016/j.molmet.2014.03.002 · Cited by 338 · see citing works
Impact of Circadian Nuclear Receptor REV-ERBα on Midbrain Dopamine Production and Mood Regulation
Chung, S., Lee, E. J., Yun, S., Choe, H. K., Park, S., Son, H. J., Kim, K., Dluzen, D. E., Lee, I., Hwang, O., et al. (2014) · Cell · doi:10.1016/j.cell.2014.03.039 · Cited by 298 · see citing works
Circadian Clocks and Metabolism
Marcheva, B., Ramsey, K. M., Peek, C. B., Affinati, A., Maury, E., & Bass, J. (2013) · Handbook of Experimental Pharmacology · doi:10.1007/978-3-642-25950-0_6 · Cited by 282 · see citing works
Circadian molecular clocks and cancer
Kelleher, F. C., Rao, A. D., & Maguire, A. (2013) · Cancer Letters · doi:10.1016/j.canlet.2013.09.040 · Cited by 276 · see citing works
Clocks, metabolism, and the epigenome
Feng, D., & Lazar, M. A. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.06.026 · Cited by 271 · see citing works
“PER2 binding promotes ERa degradation, regulates PPARg DNA binding, and coactivates PPARa-mediated transcription (Gery et al., 2007; Grimaldi et al., 2010; Schmutz et al., 2010), while CRY binding represses GR (Lamia et al., 2011).”
Daily eating patterns and their impact on health and disease
Zarrinpar, A., Chaix, A., & Panda, S. (2016) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2015.11.007 · Cited by 263 · see citing works
Delay in Feedback Repression by Cryptochrome 1 Is Required for Circadian Clock Function
Ukai‐Tadenuma, M., Yamada, R. G., Xu, H., Ripperger, J. A., Liu, A. C., & Ueda, H. R. (2011) · Cell · doi:10.1016/j.cell.2010.12.019 · Cited by 264 · see citing works
The nuclear receptor REV-ERBα is required for the daily balance of carbohydrate and lipid metabolism
Delezie, J., Dumont, S., Dardente, H., Oudart, H., Gréchez‐Cassiau, A., Klosen, P., Teboul, M., Delaunay, F., Pévet, P., & Challet, E. (2012) · The FASEB Journal · doi:10.1096/fj.12-208751 · Cited by 252 · see citing works
The forebrain synaptic transcriptome is organized by clocks but its proteome is driven by sleep
Noya, S. B., Colameo, D., Brüning, F., Spinnler, A., Mircsof, D., Opitz, L., Mann, M., Tyagarajan, S. K., Robles, M. S., & Brown, S. A. (2019) · Science · doi:10.1126/science.aav2642 · Cited by 248 · see citing works
NONO couples the circadian clock to the cell cycle
Kowalska, E., Ripperger, J. A., Hoegger, D. C., Bruegger, P., Buch, T., Birchler, T., Mueller, A., Albrecht, U., Contaldo, C., & Brown, S. A. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1213317110 · Cited by 251 · see citing works
Ye, R., Selby, C. P., Chiou, Y., Ozkan‐Dagliyan, I., Gaddameedhi, S., & Sancar, A. (2014) · Genes & Development · doi:10.1101/gad.249417.114 · Cited by 247 · see citing works
Circadian rhythms in glucose and lipid metabolism in nocturnal and diurnal mammals
Kumar Jha, P., Challet, E., & Kalsbeek, A. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.01.024 · Cited by 235 · see citing works
Mammalian circadian clock and metabolism – the epigenetic link
Bellet, M. M., & Sassone‐Corsi, P. (2010) · Journal of Cell Science · doi:10.1242/jcs.051649 · Cited by 237 · see citing works
Circadian rhythms of liver physiology and disease: experimental and clinical evidence
Tahara, Y., & Shibata, S. (2016) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2016.8 · Cited by 231 · see citing works
PPARs Integrate the Mammalian Clock and Energy Metabolism
Chen, L., & Yang, G. (2014) · PPAR Research · doi:10.1155/2014/653017 · Cited by 223 · see citing works
Regulation of metabolism: the circadian clock dictates the time
Sahar, S., & Sassone-Corsi, P. (2012) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2011.10.005 · Cited by 222 · see citing works
Circadian Etiology of Type 2 Diabetes Mellitus
Javeed, N., & Matveyenko, A. V. (2018) · Physiology · doi:10.1152/physiol.00003.2018 · Cited by 205 · see citing works
Tahara, Y., & Shibata, S. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.08.049 · Cited by 198 · see citing works
Nutrients, Clock Genes, and Chrononutrition
Oike, H., Oishi, K., & Kobori, M. (2014) · Current Nutrition Reports · doi:10.1007/s13668-014-0082-6 · Cited by 198 · see citing works
Weger, B. D., Gobet, C., David, F. P. A., Atger, F., Martín, E., Phillips, N. E., Charpagne, A., Weger, M., Naef, F., & Gachon, F. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2015803118 · Cited by 187 · see citing works
Bunney, B. G., & Bunney, W. E. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.07.020 · Cited by 181 · see citing works
Ishii, T., Warabi, E., & Mann, G. E. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.09.002 · Cited by 177 · see citing works
Circadian Rhythms in the Pathogenesis and Treatment of Fatty Liver Disease
Saran, A., Dave, S., & Zarrinpar, A. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.01.050 · Cited by 172 · see citing works
Molecular Interactions Between Components of the Circadian Clock and the Immune System
Hergenhan, S. M., Holtkamp, S., & Scheiermann, C. (2020) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.12.044 · Cited by 170 · see citing works
Evolution of circadian rhythms: from bacteria to human
Bhadra, U., Thakkar, N., Das, P., & Pal Bhadra, M. (2017) · Sleep Medicine · doi:10.1016/j.sleep.2017.04.008 · Cited by 167 · see citing works
Hwang‐Verslues, W. W., Chang, P.-H., Jeng, Y., Kuo, W., Chiang, P.-H., Chang, Y., Hsieh, T.-H., Su, F., Lin, L.-C., Abbondante, S., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1222684110 · Cited by 158 · see citing works
Chiou, Y., Yang, Y., Rashid, N. U., Ye, R., Selby, C. P., & Sancar, A. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1612917113 · Cited by 152 · see citing works
Machine Learning Helps Identify CHRONO as a Circadian Clock Component
Anafi, R. C., Lee, Y., Sato, T. K., Venkataraman, A., Ramanathan, C., Kavaklı, İ. H., Hughes, M. E., Baggs, J. E., Growe, J., Liu, A. C., et al. (2014) · PLoS Biology · doi:10.1371/journal.pbio.1001840 · Cited by 147 · see citing works
HNF4α—role in drug metabolism and potential drug target?
Hwang‐Verslues, W. W., & Sladek, F. M. (2010) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2010.08.010 · Cited by 147 · see citing works
Off the Clock: From Circadian Disruption to Metabolic Disease
Maury, E. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20071597 · Cited by 142 · see citing works
The adrenal peripheral clock: Glucocorticoid and the circadian timing system
Son, G. H., Chung, S., & Kim, K. (2011) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2011.07.003 · Cited by 136 · see citing works
Ribas‐Latre, A., & Eckel‐Mahan, K. L. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2015.12.006 · Cited by 133 · see citing works
Biochemical Analysis of the Canonical Model for the Mammalian Circadian Clock
Ye, R., Selby, C. P., Öztürk, N., Annayev, Y., & Sancar, A. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.254680 · Cited by 129 · see citing works
Interactive Features of Proteins Composing Eukaryotic Circadian Clocks
Crane, B. R., & Young, M. W. (2014) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060713-035644 · Cited by 125 · see citing works
Role of the circadian clock gene Per2 in adaptation to cold temperature
Chappuis, S., Ripperger, J. A., Schnell, A., Rando, G., Jud, C., Wahli, W., & Albrecht, U. (2013) · Molecular Metabolism · doi:10.1016/j.molmet.2013.05.002 · Cited by 125 · see citing works
Berthier, A., Johanns, M., Zummo, F. P., Lefebvre, P., & Staels, B. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2021.166097 · Cited by 125 · see citing works
Peripheral Circadian Oscillators in Mammals
Brown, S. A., & Azzi, A. (2013) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-25950-0_3 · Cited by 120 · see citing works
Liver-derived ketone bodies are necessary for food anticipation
Chavan, R., Feillet, C. A., Costa, S. S., Delorme, J. E., Okabe, T., Ripperger, J. A., & Albrecht, U. (2016) · Nature Communications · doi:10.1038/ncomms10580 · Cited by 124 · see citing works
Spatiotemporal Metabolic Liver Zonation and Consequences on Pathophysiology
Martini, T., Naef, F., & Tchorz, J. S. (2023) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-031521-024831 · Cited by 113 · see citing works
Glucocorticoid-mediated Period2 induction delays the phase of circadian rhythm
Cheon, S., Park, N., Cho, S., & Kim, K. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt307 · Cited by 119 · see citing works
Interactions between metabolism and circadian clocks: reciprocal disturbances
Delezie, J., & Challet, É. (2011) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2011.06246.x · Cited by 118 · see citing works
Circadian Metabolism: From Mechanisms to Metabolomics and Medicine
Brown, S. A. (2016) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2016.03.015 · Cited by 118 · see citing works
CRY1/2 Selectively Repress PPARδ and Limit Exercise Capacity
Jordan, S. D., Kriebs, A., Vaughan, M. E., Duglan, D., Fan, W., Henriksson, E., Huber, A., Papp, S. J., Nguyen, M., Afetian, M. E., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.06.002 · Cited by 112 · see citing works
Ramanathan, C., Xu, H., Khan, S. K., Shen, Y., Gitis, P. J., Welsh, D. K., Hogenesch, J. B., & Liu, A. C. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004244 · Cited by 108 · see citing works
Nuclear receptors rock around the clock
Zhao, X., Cho, H., Yu, R. T., Atkins, A. R., Downes, M., & Evans, R. M. (2014) · EMBO Reports · doi:10.1002/embr.201338271 · Cited by 108 · see citing works
The Nuclear Receptor REV-ERBα Regulates Fabp7 and Modulates Adult Hippocampal Neurogenesis
Schnell, A., Chappuis, S., Schmutz, I., Brai, E., Ripperger, J. A., Schaad, O., Welzl, H., Descombes, P., Alberi, L. A., & Albrecht, U. (2014) · PLoS ONE · doi:10.1371/journal.pone.0099883 · Cited by 104 · see citing works
Nutrient sensing and the circadian clock
Peek, C. B., Ramsey, K. M., Marcheva, B., & Bass, J. T. (2012) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2012.02.003 · Cited by 103 · see citing works
Kriebs, A., Jordan, S. D., Soto, E., Henriksson, E., Sandate, C. R., Vaughan, M. E., Chan, A. B., Duglan, D., Papp, S. J., Huber, A., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1704955114 · Cited by 105 · see citing works
Circadian autophagy rhythm: a link between clock and metabolism?
Ma, D., Li, S., Molusky, M. M., & Lin, J. D. (2012) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2012.03.004 · Cited by 103 · see citing works
Genomic Convergence among ERRα, PROX1, and BMAL1 in the Control of Metabolic Clock Outputs
Dufour, C. R., Levasseur, M.-P., Pham, N. H. H., Eichner, L. J., Wilson, B. J., Charest-Marcotte, A., Duguay, D., Poirier-Héon, J.-F., Cermakian, N., & Giguère, V. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002143 · Cited by 102 · see citing works
Clock gene variants in mood and anxiety disorders
Partonen, T. (2012) · Journal of Neural Transmission · doi:10.1007/s00702-012-0810-2 · Cited by 99 · see citing works
Zmrzljak, U. P., & Rozman, D. (2012) · Chemical Research in Toxicology · doi:10.1021/tx200538r · Cited by 97 · see citing works
Circadian regulation of liver function: from molecular mechanisms to disease pathophysiology
Bolshette, N. B., Ibrahim, H., Reinke, H., & Asher, G. (2023) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00792-1 · Cited by 99 · see citing works
Wang, T., Wang, Z., Yang, P., Xia, L., Zhou, M., Wang, S., Du, J., & Zhang, J. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.9 · Cited by 96 · see citing works
Chrono-biology, Chrono-pharmacology and Chrono-nutrition
Tahara, Y., & Shibata, S. (2014) · Journal of Pharmacological Sciences · doi:10.1254/jphs.13r06cr · Cited by 94 · see citing works
Nuclear receptor signal transduction in C. elegans
Antebi, A. (2015) · WormBook · doi:10.1895/wormbook.1.64.2 · Cited by 92 · see citing works
Ripperger, J. A., Jud, C., & Albrecht, U. (2011) · FEBS Letters · doi:10.1016/j.febslet.2011.02.027 · Cited by 93 · see citing works
The Circadian Clock in Oral Health and Diseases
Papagerakis, S. M., Zheng, L., Schnell, S. D., Sartor, M., Somers, E. C., Marder, W., McAlpin, B. R., Kim, D. W., McHugh, J. B., & Papagerakis, P. (2013) · Journal of Dental Research · doi:10.1177/0022034513505768 · Cited by 93 · see citing works
Emerging Models for the Molecular Basis of Mammalian Circadian Timing
Gustafson, C. L., & Partch, C. L. (2014) · Biochemistry · doi:10.1021/bi500731f · Cited by 88 · see citing works
Circadian rhythms in the blood–brain barrier: impact on neurological disorders and stress responses
Schurhoff, N. A., & Toborek, M. J. (2023) · Molecular Brain · doi:10.1186/s13041-023-00997-0 · Cited by 91 · see citing works
The circadian mutation PER2S662G is linked to cell cycle progression and tumorigenesis
Gu, X., Xing, L., Shi, G., Liu, Z., Wang, X., Qu, Z., Wu, X., Dong, Z., Gao, X., Liu, G., et al. (2011) · Cell Death and Differentiation · doi:10.1038/cdd.2011.103 · Cited by 89 · see citing works
Circadian oscillator proteins across the kingdoms of life: structural aspects
Saini, R. V., Jaskólski, M., & Davis, S. J. (2019) · BMC Biology · doi:10.1186/s12915-018-0623-3 · Cited by 88 · see citing works
Filiano, A. N., Millender-Swain, T., Johnson, R., Young, M. E., Gamble, K. L., & Bailey, S. M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0071684 · Cited by 88 · see citing works
Circadian Clocks and Mood-Related Behaviors
Albrecht, U. (2013) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-25950-0_9 · Cited by 86 · see citing works
Circadian Rhythm Gene Period 3 Is an Inhibitor of the Adipocyte Cell Fate
Costa, M. J. D. C., So, A. Y., Kaasik, K., Krueger, K. C., Pillsbury, M. L., Fu, Y., Ptáček, L. J., Yamamoto, K. R., & Feldman, B. J. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.164558 · Cited by 83 · see citing works
The circadian clock, metabolism and obesity
Albrecht, U. (2017) · Obesity Reviews · doi:10.1111/obr.12502 · Cited by 83 · see citing works
Nuclear receptor HNF4A transrepresses CLOCK:BMAL1 and modulates tissue-specific circadian networks
Qu, M., Duffy, T., Hirota, T., & Kay, S. A. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1816411115 · Cited by 82 · see citing works
Endocrine regulation of circadian physiology
Tsang, A. H. K., Astiz, M., Friedrichs, M., & Oster, H. (2016) · Journal of Endocrinology · doi:10.1530/joe-16-0051 · Cited by 82 · see citing works
Potential Roles of Dec and Bmal1 Genes in Interconnecting Circadian Clock and Energy Metabolism
Sato, F., Kohsaka, A., BHAWAL, U. K., & Muragaki, Y. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19030781 · Cited by 78 · see citing works
The PPAR–microbiota–metabolic organ trilogy to fine‐tune physiology
Oh, H. Y. P., Visvalingam, V., & Wahli, W. (2019) · The FASEB Journal · doi:10.1096/fj.201802681rr · Cited by 78 · see citing works
The emerging roles of lipids in circadian control
Adamovich, Y., Aviram, R., & Asher, G. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2014.11.013 · Cited by 78 · see citing works
Zani, F., Breasson, L., Becattini, B., Vukolic, A., Montani, J.-P., Albrecht, U., Provenzani, A., Ripperger, J. A., & Solinas, G. (2013) · Molecular Metabolism · doi:10.1016/j.molmet.2013.06.006 · Cited by 75 · see citing works
Circadian Clocks and Metabolism: Implications for Microbiome and Aging
Paschos, G. K., & FitzGerald, G. A. (2017) · Trends in Genetics · doi:10.1016/j.tig.2017.07.010 · Cited by 77 · see citing works
CREBH Couples Circadian Clock With Hepatic Lipid Metabolism
Zheng, Z., Kim, H., Qiu, Y., Chen, X., Méndez, R., Dandekar, A. P., Zhang, X., Zhang, C., Liu, A. C., Yin, L., et al. (2016) · Diabetes · doi:10.2337/db16-0298 · Cited by 77 · see citing works
Circadian clock dysfunction in human omental fat links obesity to metabolic inflammation
Maury, E., Navez, B., & Brichard, S. M. (2021) · Nature Communications · doi:10.1038/s41467-021-22571-9 · Cited by 77 · see citing works
SRC-2 Is an Essential Coactivator for Orchestrating Metabolism and Circadian Rhythm
Stashi, E., Lanz, R. B., Mao, J., Michailidis, G. C., Zhu, B., Kettner, N. M., Putluri, N., Reineke, E. L., Reineke, L. C., Dasgupta, S., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.01.027 · Cited by 76 · see citing works
Bellet, M. M., Masri, S., Astarita, G., Sassone‐Corsi, P., Fazia, M. A. D., & Servillo, G. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.737114 · Cited by 76 · see citing works
Kucera, N., Schmalen, I., Hennig, S., Öllinger, R., Strauss, H. M., Grudziecki, A., Wieczorek, C. M., Kramer, A., & Wolf, E. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1113280109 · Cited by 74 · see citing works
PER1 Phosphorylation Specifies Feeding Rhythm in Mice
Liu, Z., Huang, M., Wu, X., Shi, G., Xing, L., Dong, Z., Qu, Z., Yan, J., Yang, L., Panda, S., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.04.032 · Cited by 73 · see citing works
Bonney, S. K., Kominsky, D., Brodsky, K. S., Eltzschig, H. K., Walker, L. A., & Eckle, T. D. L. G. (2013) · PLoS ONE · doi:10.1371/journal.pone.0071493 · Cited by 74 · see citing works
Fatty-Acid Binding Proteins Modulate Sleep and Enhance Long-Term Memory Consolidation in Drosophila
Gerstner, J. R., Vanderheyden, W. M., Shaw, P. J., Landry, C. F., & Yin, J. C. P. (2011) · PLoS ONE · doi:10.1371/journal.pone.0015890 · Cited by 71 · see citing works
Regulation of αENaC expression by the circadian clock protein Period 1 in mpkCCDc14 cells
Gumz, M. L., Cheng, K., Lynch, I. J., Stow, L. R., Greenlee, M. M., Cain, B. D., & Wingo, C. S. (2010) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2010.09.003 · Cited by 72 · see citing works
Rossetti, S., Esposito, J., Corlazzoli, F., Gregorski, A., & Sacchi, N. (2012) · Cell Cycle · doi:10.4161/cc.11.2.18792 · Cited by 71 · see citing works
Annayev, Y., Adar, S., Chiou, Y., Lieb, J. D., Sancar, A., & Ye, R. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.534651 · Cited by 73 · see citing works
- Authors
- Schmutz, I., Ripperger, J. A., Baeriswyl-Aebischer, S., & Albrecht, U.
- Affiliations
- University of Fribourg (CH)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2010-02-15
- Volume
- 24
- Issue
- 4
- Pages
- 345-357
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC2816734
- OpenAlex
- W2122503953
- Cited by
- 361
- References
- 64
- Citations by year
- 2026: 6 · 2025: 22 · 2024: 12 · 2023: 17 · 2022: 19 · 2021: 26 · 2020: 14 · 2019: 21 · 2018: 14 · 2017: 21 · 2016: 23 · 2015: 23 · 2014: 37 · 2013: 30 · 2012: 35
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- reroDoc Digital Library (submittedVersion)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Light effects on plants
- Keywords
- Per2, circadian clock, nuclear receptors, PPARα, NR1D1, co-regulation, transcriptional repression, Bmal1, HNF1A, glucose-6-phosphatase, promoter binding
- MeSH terms
- Animals, Circadian Rhythm, Gene Expression Regulation, Glucose, Liver, Promoter Regions, Genetic, Protein Binding, Receptors, Cytoplasmic and Nuclear, Mice, Knockout, Amino Acid Motifs, NIH 3T3 Cells, PPAR alpha, Mice, ARNTL Transcription Factors, Period Circadian Proteins, Nuclear Receptor Subfamily 1, Group D, Member 1
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