System-Driven and Oscillator-Dependent Circadian Transcription in Mice with a Conditionally Active Liver Clock
Open accessAbstract
The mammalian circadian timing system consists of a master pacemaker in neurons of the suprachiasmatic nucleus (SCN) and clocks of a similar molecular makeup in most peripheral body cells. Peripheral oscillators are self-sustained and cell autonomous, but they have to be synchronized by the SCN to ensure phase coherence within the organism. In principle, the rhythmic expression of genes in peripheral organs could thus be driven not only by local oscillators, but also by circadian systemic signals. To discriminate between these mechanisms, we engineered a mouse strain with a conditionally active liver clock, in which REV-ERBalpha represses the transcription of the essential core clock gene Bmal1 in a doxycycline-dependent manner. We examined circadian liver gene expression genome-wide in mice in which hepatocyte oscillators were either running or arrested, and found that the rhythmic transcription of most genes depended on functional hepatocyte clocks. However, we discovered 31 genes, including the core clock gene mPer2, whose expression oscillated robustly irrespective of whether the liver clock was running or not. By contrast, in liver explants cultured in vitro, circadian cycles of mPer2::luciferase bioluminescence could only be observed when hepatocyte oscillators were operational. Hence, the circadian cycles observed in the liver of intact animals without functional hepatocyte oscillators were likely generated by systemic signals. The finding that rhythmic mPer2 expression can be driven by both systemic cues and local oscillators suggests a plausible mechanism for the phase entrainment of subsidiary clocks in peripheral organs.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In a mouse model, about 10% of rhythmically expressed liver genes were not under control of hepatocyte clocks but instead relied on oscillatory systemic signals.
“This was suggested in a mouse model, engineered to differentiate between central and peripheral entrainment cues, where the authors showed that about 10% of rhythmically expressed liver genes were not under control of hepatocyte clocks but instead relied on oscillatory systemic signals54.”
From Diurnal rhythms of wrist temperature are associated with future disease risk in the UK Biobank (2023) · cites this paper as [54]
These oscillatory temperature cues are likely picked up in the periphery to entrain, for example, sets of hepatic gene transcripts independent of peripheral liver clocks.
“These oscillatory temperature cues are likely picked up in the periphery to entrain, for example, sets of hepatic gene transcripts independent of peripheral liver clocks54.”
From Diurnal rhythms of wrist temperature are associated with future disease risk in the UK Biobank (2023) · cites this paper as [54]
Rhythmic feeding is both necessary and sufficient to drive the circadian expression of liver genes.
“Indeed, it was shown that rhythmic feeding is both necessary and sufficient to drive the circadian expression of liver genes [7,8]”
From Circadian control of glucose metabolism (2014) · cites this paper as [8]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Church, G. M., & Gilbert, W. (1984) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.81.7.1991 · Cited by 8,213 · see citing works
Bolstad, B. M., Irizarry, R. A., Åstrand, M., & Speed, T. P. (2003) · Bioinformatics · doi:10.1093/bioinformatics/19.2.185 · Cited by 8,185 · see citing works
Coordination of circadian timing in mammals
Reppert, S. M., & Weaver, D. R. (2002) · Nature · doi:10.1038/nature00965 · Cited by 4,379 · see citing works
Damiola, F., Le Minh, N., Preitner, N., Kornmann, B., Fleury-Olela, F., & Schibler, U. (2000) · Genes & Development · doi:10.1101/gad.183500 · Cited by 2,394 · see citing works
Self-citationYoo, S.-H., Yamazaki, S., Lowrey, P. L., Shimomura, K., Ko, C. H., Buhr, E. D., Siepka, S. M., Hong, H.-K., Oh, W. J., Yoo, O. J., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308709101 · Cited by 2,329 · see citing works
Self-citationCoordinated 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
Self-citationPreitner, 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
Self-citationManipulating the Mouse Embryo: A Laboratory Manual
Behringer, R. R., Gertsenstein, M., Nagy, K. V., & Nagy, A. (2002) · Cited by 2,046 · see citing works
Morimoto, R. I. (1998) · Genes & Development · doi:10.1101/gad.12.24.3788 · Cited by 1,898 · 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
Self-citationEntrainment of the circadian clock in the liver by feeding
Stokkan, K.-A., Yamazaki, S., Tei, H., Sakaki, Y., & Menaker, M. (2001) · Science · doi:10.1126/science.291.5503.490 · Cited by 1,800 · 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
Self-citationExtensive 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
Zou, J., Guo, Y., Guettouche, T., Smith, D. F., & Voellmy, R. W. (1998) · Cell · doi:10.1016/s0092-8674(00)81588-3 · Cited by 1,232 · 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
CORRELATED MORPHOMETRIC AND BIOCHEMICAL STUDIES ON THE LIVER CELL
Weibel, E. R., Stäubli, W., Gnägi, H. R., & Hess, F. A. (1969) · The Journal of Cell Biology · doi:10.1083/jcb.42.1.68 · Cited by 1,142 · 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
Self-citationRoles of the heat shock transcription factors in regulation of the heat shock response and beyond
Pirkkala, L., NYKÄNEN, P., & Sistonen, L. (2001) · The FASEB Journal · doi:10.1096/fj00-0294rev · Cited by 996 · 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
Blouin, A., Bolender, R. P., & Weibel, E. R. (1977) · The Journal of Cell Biology · doi:10.1083/jcb.72.2.441 · Cited by 866 · see citing works
A 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
Doxycycline-mediated quantitative and tissue-specific control of gene expression in transgenic mice.
Kistner, A., Gossen, M., Zimmermann, F., Jerecic, J., Ullmer, C., Lübbert, H., & Bujard, H. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.20.10933 · Cited by 780 · see citing works
Self-citationAkhtar, R. A., Reddy, A. B., Maywood, E. S., Clayton, J. D., King, V. M., Smith, A. G., Gant, T. W., Hastings, M. H., & Kyriacou, C. P. (2002) · Current Biology · doi:10.1016/s0960-9822(02)00759-5 · Cited by 777 · see citing works
Welsh, D. K., Yoo, S.-H., Liu, A. C., Takahashi, J. S., & Kay, S. A. (2004) · Current Biology · doi:10.1016/j.cub.2004.11.057 · Cited by 726 · see citing works
Self-citationRipperger, J. A., & Schibler, U. (2006) · Nature Genetics · doi:10.1038/ng1738 · Cited by 593 · see citing works
Self-citationRhythms of Mammalian Body Temperature Can Sustain Peripheral Circadian Clocks
Brown, S. A., Zumbrunn, G., Fleury-Olela, F., Preitner, N., & Schibler, U. (2002) · Current Biology · doi:10.1016/s0960-9822(02)01145-4 · Cited by 589 · see citing works
Self-citationThe orphan nuclear receptor RORα regulates circadian transcription of the mammalian core-clock Bmal1
Akashi, M., & Takumi, T. (2005) · Nature Structural & Molecular Biology · doi:10.1038/nsmb925 · Cited by 493 · see citing works
Glucocorticoid hormones inhibit food‐induced phase‐shifting of peripheral circadian oscillators
Minh, N. L., Damiola, F., Tronche, F., Schütz, G., & Schibler, U. (2001) · The EMBO Journal · doi:10.1093/emboj/20.24.7128 · Cited by 467 · see citing works
Self-citationA clock shock: mouse CLOCK is not required for circadian oscillator function
DeBruyne, J. P., Noton, E., Lambert, C. M., Maywood, E. S., Weaver, D. R., & Reppert, S. M. (2006) · Neuron · doi:10.1016/j.neuron.2006.03.041 · Cited by 430 · see citing works
A Glycine-rich RNA-binding Protein Mediating Cold-inducible Suppression of Mammalian Cell Growth
Nishiyama, H., Itoh, K., Kaneko, Y., et al. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.137.4.899 · Cited by 392 · see citing works
Feedback repression is required for mammalian circadian clock function
Sato, T. K., Yamada, R. G., Ukai, H., Baggs, J. E., Miraglia, L. J., Kobayashi, T., Welsh, D. K., Kay, S. A., Ueda, H. R., & Hogenesch, J. B. (2006) · Nature Genetics · doi:10.1038/ng1745 · Cited by 373 · see citing works
Trinklein, N. D., Murray, J. I., Hartman, S. J., Botstein, D., & Myers, R. (2003) · Molecular Biology of the Cell · doi:10.1091/mbc.e03-10-0738 · Cited by 341 · see citing works
Phosphorylation of serine 230 promotes inducible transcriptional activity of heat shock factor 1
Holmberg, C. I., Hietakangas, V., Mikhailov, A., Rantanen, J. O., Kallio, M. J., Meinander, A., Hellman, J., Morrice, N., MacKintosh, C., Morimoto, R. I., et al. (2001) · The EMBO Journal · doi:10.1093/emboj/20.14.3800 · Cited by 333 · see citing works
The Circadian Regulatory Proteins BMAL1 and Cryptochromes Are Substrates of Casein Kinase Iε
Eide, E. J., Vielhaber, E. L., Hinz, W. A., & Virshup, D. M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111466200 · Cited by 301 · see citing works
Lavery, D. J., & Schibler, U. (1993) · Genes & Development · doi:10.1101/gad.7.10.1871 · Cited by 300 · see citing works
Self-citationThe loss of circadian PAR bZip transcription factors results in epilepsyPreprint
Gachon, F., Fonjallaz, P., Damiola, F., Gos, P., Kodama, T., Zákány, J., Duboule, D., Petit, B., Tafti, M., & Schibler, U. (2004) · Genes & Development · doi:10.1101/gad.301404 · Cited by 285 · see citing works
Self-citationNeurotransmitters of the retino-hypothalamic tract
Hannibal, J. (2002) · Cell and Tissue Research · doi:10.1007/s00441-002-0574-3 · Cited by 275 · see citing works
Wellmann, S. M., Bührer, C., Moderegger, E., Marten, A., Kirschner‐Schwabe, R., Koehne, P. S., Fujita, J., & Seeger, K. (2004) · Journal of Cell Science · doi:10.1242/jcs.01026 · Cited by 257 · see citing works
Nocturnin, a Deadenylase in Xenopus laevis Retina
Baggs, J. E., & Green, C. B. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00014-9 · Cited by 175 · see citing works
Morimoto, R. I., Kroeger, P. E., & Cotto, J. J. (1996) · Birkhäuser Basel eBooks · doi:10.1007/978-3-0348-9088-5_10 · Cited by 167 · see citing works
The orphan receptor Rev-erb α gene is a target of the circadian clock pacemaker
Triqueneaux, G., Thénot, S., Kakizawa, T., Antoch, M. P., Safi, R., Takahashi, J. S., Delaunay, F., & Laudet, V. (2004) · Journal of Molecular Endocrinology · doi:10.1677/jme.1.01554 · Cited by 166 · see citing works
Self-citationFonjallaz, P., Ossipow, V., Wanner, G., & Schibler, U. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00365.x · Cited by 151 · see citing works
Self-citationRobust detection of periodic time series measured from biological systems
Ahdesmaki, M. J., Lähdesmäki, H. J., Pearson, R., Huttunen, H. J., & Yli-Harja, O. P. (2005) · BMC Bioinformatics · doi:10.1186/1471-2105-6-117 · Cited by 134 · see citing works
Rhythmic expression of NocturninmRNA in multiple tissues of the mouse
Wang, Y., Osterbur, D., Megaw, P. L., Tosini, G., Fukuhara, C., Green, C. B., & Besharse, J. C. (2001) · BMC Developmental Biology · doi:10.1186/1471-213x-1-9 · Cited by 120 · see citing works
Kornmann, B. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.11.e51 · Cited by 119 · see citing works
Self-citationPhase Responses to Light Pulses in Mice Lacking Functional per or cry Genes
Spoelstra, K., Albrecht, U., van der Horst, G. T. J., Brauer, V. S., & Daan, S. (2004) · Journal of Biological Rhythms · doi:10.1177/0748730404268122 · Cited by 107 · see citing works
Serine phosphorylation of mCRY1 and mCRY2 by mitogen‐activated protein kinase
Sanada, K., Harada, Y., Sakai, M., Todo, T., & Fukada, Y. (2004) · Genes to Cells · doi:10.1111/j.1356-9597.2004.00758.x · Cited by 69 · see citing works
Circadian Gene Expression in Cultured Cells
Nagoshi, E., Brown, S. A., Dibner, C., Kornmann, B., & Schibler, U. (2005) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(05)93028-0 · Cited by 67 · see citing works
Self-citationDiurnal Change of the Cold-Inducible RNA-Binding Protein (Cirp) Expression in Mouse Brain
Nishiyama, H., Xue, J.-H., Sato, T., et al. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.8482 · Cited by 67 · see citing works
Second messenger and Ras/MAPK signalling pathways regulate CLOCK/CYCLE‐dependent transcription
Weber, F., Hung, H., Maurer, C., & Kay, S. A. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.03865.x · Cited by 60 · see citing works
Molecular and Statistical Tools for Circadian Transcript Profiling
Wijnen, H., Naef, F., & Young, M. W. (2005) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(05)93015-2 · Cited by 56 · see citing works
Sundgren‐Andersson, A. K., Östlund, P., & Bartfai, T. (1998) · NeuroImmunoModulation · doi:10.1159/000026344 · Cited by 32 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Dibner, C., Schibler, U., & Albrecht, U. (2010) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021909-135821 · Cited by 2,421 · see citing works
Self-citationAdverse metabolic and cardiovascular consequences of circadian misalignment
Scheer, F. A. J. L., Hilton, M. F., Mantzoros, C. S., & Shea, S. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808180106 · Cited by 2,351 · see citing works
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
Self-citationHatori, M., Vollmers, C., Zarrinpar, A., DiTacchio, L., Bushong, E. A., Gill, S., Leblanc, M., Chaix, A., Joens, M., Fitzpatrick, J. A. J., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.019 · Cited by 1,986 · 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
Self-citationThe genetics of mammalian circadian order and disorder: implications for physiology and disease
Takahashi, J. S., Hong, H.-K., Ko, C. H., & McDearmon, E. L. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2430 · Cited by 1,611 · see citing works
Self-citationDisruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes
Marcheva, B., Ramsey, K. M., Buhr, E. D., Kobayashi, Y., Su, H., Ko, C. H., Ivanova, G., Omura, C., Mo, S., Vitaterna, M. H., et al. (2010) · Nature · doi:10.1038/nature09253 · Cited by 1,525 · see citing works
Self-citationMolecular 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
Self-citationSIRT1 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
Self-citationSuprachiasmatic Nucleus: Cell Autonomy and Network Properties
Welsh, D. K., Takahashi, J. S., & Kay, S. A. (2010) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021909-135919 · Cited by 1,216 · see citing works
Self-citationPhysiological 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
Temperature as a Universal Resetting Cue for Mammalian Circadian Oscillators
Buhr, E. D., Yoo, S.-H., & Takahashi, J. S. (2010) · Science · doi:10.1126/science.1195262 · Cited by 917 · see citing works
Self-citationTiming 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
Green, C. B., Takahashi, J. S., & Bass, J. (2008) · Cell · doi:10.1016/j.cell.2008.08.022 · Cited by 902 · see citing works
Self-citationA circadian clock in macrophages controls inflammatory immune responses
Keller, M., Mazuch, J., Abraham, U., Eom, G. D., Herzog, E. D., Volk, H.-D., Kramer, A., & Maier, B. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0906361106 · Cited by 843 · see citing works
Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression.
Vollmers, C., Gill, S., DiTacchio, L., Pulivarthy, S. R., Le, H. D., & Panda, S. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909591106 · Cited by 765 · see citing works
Molecular components of the mammalian circadian clock
Buhr, E. D., & Takahashi, J. S. (2013) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-25950-0_1 · Cited by 738 · see citing works
Self-citationCircadian clocks and insulin resistance
Stenvers, D. J., Scheer, F. A. J. L., Schrauwen, P., la Fleur, S. E., & Kalsbeek, A. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0122-1 · Cited by 733 · 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
Self-citationCryptochromes 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
The Functional and Clinical Significance of the 24-Hour Rhythm of Circulating Glucocorticoids
Oster, H., Challet, E., Ott, V., Arvat, E., de Kloet, E. R., Dijk, D.-J., Lightman, S., Vgontzas, A., & Van Cauter, E. (2017) · Endocrine Reviews · doi:10.1210/er.2015-1080 · Cited by 548 · see citing works
Dysregulation of inflammatory responses by chronic circadian disruption
Castanon-Cervantes, O., Wu, M., Ehlen, J. C., Paul, K., Gamble, K. L., Johnson, R. L., Besing, R. C., Menaker, M., Gewirtz, A. T., & Davidson, A. J. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1001026 · Cited by 542 · see citing works
Metabolism and Circadian Rhythms—Implications for Obesity
Froy, O. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0014 · Cited by 505 · see citing works
Glucocorticoids and the circadian clock
Dickmeis, T. (2009) · Journal of Endocrinology · doi:10.1677/joe-08-0415 · Cited by 494 · see citing works
Obesity in mice with adipocyte-specific deletion of clock component Arntl
Paschos, G. K., Ibrahim, S., Song, W.-L., Kunieda, T., Grant, G., Reyes, T. M., Bradfield, C. A., Vaughan, C. H., Eiden, M., Masoodi, M., et al. (2012) · Nature Medicine · doi:10.1038/nm.2979 · Cited by 465 · see citing works
Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic muscle clock
Dyar, K. A., Ciciliot, S., Wright, L. E., Biensø, R. S., Tagliazucchi, G. M., Patel, V. R., Forcato, M., Paz, M. I. P., Gudiksen, A., Solagna, F., et al. (2014) · Molecular Metabolism · doi:10.1016/j.molmet.2013.10.005 · Cited by 454 · see citing works
Circadian clocks: regulators of endocrine and metabolic rhythms
Hastings, M., O’Neill, J. S., & Maywood, E. S. (2007) · Journal of Endocrinology · doi:10.1677/joe-07-0378 · Cited by 426 · see citing works
Mistimed sleep disrupts circadian regulation of the human transcriptome
Archer, S. N., Laing, E. E., Möller-Levet, C. S., van der Veen, D. R., Bucca, G., Lazar, A. S., Santhi, N., Slak, A., Kabiljo, R., von Schantz, M., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1316335111 · Cited by 386 · see citing works
Time-restricted eating for the prevention and management of metabolic diseases
Manoogian, E. N. C., Chow, L. S., Taub, P. R., Laferrère, B., & Panda, S. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnab027 · Cited by 344 · see citing works
Poly(ADP-ribose) polymerase 1 participates in the phase entrainment of circadian clocks to feeding
Asher, G., Reinke, H., Altmeyer, M., Gutierrez-Arcelus, M., Hottiger, M. O., & Schibler, U. (2010) · Cell · doi:10.1016/j.cell.2010.08.016 · Cited by 340 · see citing works
Self-citationCircadian 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
Circadian Clock Control of Liver Metabolic Functions
Reinke, H., & Asher, G. (2016) · Gastroenterology · doi:10.1053/j.gastro.2015.11.043 · Cited by 321 · see citing works
Sadacca, L. A., Lamia, K. A., deLemos, A. S., Blum, B., & Weitz, C. J. (2011) · Diabetologia · doi:10.1007/s00125-010-1920-8 · Cited by 314 · see citing works
Health Consequences of Circadian Disruption in Humans and Animal Models
Evans, J. A., & Davidson, A. J. (2013) · Progress in Molecular Biology and Translational Science · doi:10.1016/b978-0-12-396971-2.00010-5 · Cited by 291 · 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
Liver zonation: Novel aspects of its regulation and its impact on homeostasis
Gebhardt, R. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i26.8491 · Cited by 275 · see citing works
Molecular clock is involved in predictive circadian adjustment of renal function
Zuber, A. M., Centeno, G., Pradervand, S., Nikolaeva, S., Maquelin, L., Cardinaux, L., Bonny, O., & Firsov, D. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904890106 · Cited by 274 · 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
“Liver-specific overexpression of REV-ERBa abolishes oscillation of almost all the rhythmic transcripts found in wild-type mice, suggesting that they are controlled by the liver clock (Kornmann et al., 2007).”
Neufeld-Cohen, A., Robles, M. S., Aviram, R., Manella, G., Adamovich, Y., Ladeuix, B., Nir, D., Rousso-Noori, L., Kuperman, Y., Golik, M., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1519650113 · Cited by 262 · see citing works
Circadian timing of metabolism in animal models and humans
Dibner, C., & Schibler, U. (2015) · Journal of Internal Medicine · doi:10.1111/joim.12347 · Cited by 237 · see citing works
Self-citationMoon, S., Kang, J., Kim, S. H., Chung, H. S., Kim, Y. J., Yu, J. M., Cho, S. T., Oh, C.-M., & Kim, T. (2020) · Nutrients · doi:10.3390/nu12051267 · Cited by 231 · see citing works
Molecular components of the circadian clock in mammals
Takahashi, J. S. (2015) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.12514 · Cited by 230 · see citing works
Self-citationImpact of nutrients on circadian rhythmicity
Oosterman, J. E., Kalsbeek, A., la Fleur, S. E., & Belsham, D. D. (2015) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00322.2014 · Cited by 221 · see citing works
Circadian disruption and metabolic disease: Findings from animal models
Arble, D. M., Ramsey, K. M., Bass, J., & Turek, F. W. (2010) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2010.08.003 · Cited by 192 · see citing works
Blood-Borne Circadian Signal Stimulates Daily Oscillations in Actin Dynamics and SRF Activity
Gerber, A., Esnault, C., Aubert, G., Treisman, R., Pralong, F., & Schibler, U. (2013) · Cell · doi:10.1016/j.cell.2012.12.027 · Cited by 160 · see citing works
Self-citationCircadian rhythms – from genes to physiology and disease
Bollinger, T., & Schibler, U. (2014) · Swiss Medical Weekly · doi:10.4414/smw.2014.13984 · Cited by 152 · see citing works
Self-citationCircadian Rhythms, Aging, and Life Span in Mammals
Froy, O. (2011) · Physiology · doi:10.1152/physiol.00012.2011 · Cited by 156 · see citing works
Space-time logic of liver gene expression at sub-lobular scale
Droin, C., Kholtei, J. E., Bahar Halpern, K., Hurni, C., Rozenberg, M., Muvkadi, S., Itzkovitz, S., & Naef, F. (2021) · Nature Metabolism · doi:10.1038/s42255-020-00323-1 · Cited by 148 · see citing works
The circadian clock and glucocorticoids – interactions across many time scales
Dickmeis, T., Weger, B. D., & Weger, M. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.05.012 · Cited by 144 · 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
A role for clock genes in sleep homeostasis
Franken, P. (2013) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2013.05.002 · Cited by 125 · see citing works
Mongrain, V., La Spada, F., Curie, T., & Franken, P. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026622 · Cited by 118 · see citing works
Lipids around the Clock: Focus on Circadian Rhythms and Lipid Metabolism
Gnocchi, D., Pedrelli, M., Hurt-Camejo, E., & Parini, P. (2015) · Biology · doi:10.3390/biology4010104 · Cited by 115 · see citing works
Homeostatic and circadian contribution to EEG and molecular state variables of sleep regulation
Curie, T., Mongrain, V., Dorsaz, S., Mang, G. M., Emmenegger, Y., & Franken, P. (2013) · SLEEP · doi:10.5665/sleep.2440 · Cited by 94 · see citing works
Molecular aspects of circadian pharmacology and relevance for cancer chronotherapy
Ozturk, N., Ozturk, D., Kavakli, I. H., & Okyar, A. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18102168 · Cited by 106 · see citing works
Reznick, J., Preston, E., Wilks, D. L., Beale, S. M., Turner, N., & Cooney, G. J. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2012.08.010 · Cited by 86 · see citing works
Varcoe, T. J., Boden, M. J., Voultsios, A., Salkeld, M. D., Rattanatray, L., & Kennaway, D. J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0053800 · 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
Select cognitive deficits in vasoactive intestinal peptide deficient mice
Chaudhury, D., Loh, D. H., Dragich, J. M., Hagopian, A., & Colwell, C. S. (2008) · BMC Neuroscience · doi:10.1186/1471-2202-9-63 · Cited by 73 · see citing works
Hasan, S., Santhi, N., Lazar, A. S., Slak, A., Lo, J., von Schantz, M., Archer, S. N., Johnston, J. D., & Dijk, D. (2012) · The FASEB Journal · doi:10.1096/fj.11-201699 · Cited by 68 · see citing works
Seasonal changes in mood and behavior are linked to metabolic syndrome
Rintamäki, R., Grimaldi, S., Englund, A., Haukka, J., Partonen, T., Reunanen, A., Aromaa, A., & Lönnqvist, J. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001482 · Cited by 61 · see citing works
Central and peripheral circadian clocks and their role in Alzheimer's disease
Chauhan, R., Chen, K.-F., Kent, B. A., & Crowther, D. C. (2017) · Disease Models & Mechanisms · doi:10.1242/dmm.030627 · Cited by 58 · see citing works
“This was demonstrated in a mouse model in which the liver clock was specifically suppressed, resulting in all but a handful of genes losing their circadian regulation (Kornmann et al., 2007).”
BackgroundCircadian transcription from beta cell function to diabetes pathophysiology
Perelis, M., Ramsey, K. M., Marcheva, B., & Bass, J. (2016) · Journal of Biological Rhythms · doi:10.1177/0748730416656949 · Cited by 57 · see citing works
Diurnal rhythms of wrist temperature are associated with future disease risk in the UK Biobank
Brooks, T. G., Lahens, N. F., Grant, G. R., Sheline, Y. I., FitzGerald, G. A., & Skarke, C. (2023) · Nature Communications · doi:10.1038/s41467-023-40977-5 · Cited by 57 · see citing works
Circadian Redox and Metabolic Oscillations in Mammalian Systems
O'Neill, J. S., & Feeney, K. A. (2014) · Antioxidants & Redox Signaling · doi:10.1089/ars.2013.5582 · Cited by 51 · see citing works
Circadian clocks: an overview on its adaptive significance
Krittika, S., & Yadav, P. (2020) · Biological Rhythm Research · doi:10.1080/09291016.2019.1581480 · Cited by 50 · see citing works
Vitaterna, M. H., Shimomura, K., & Jiang, P. (2019) · Neurologic Clinics · doi:10.1016/j.ncl.2019.05.002 · Cited by 36 · see citing works
The Liver in the Eyes of a Chronobiologist
Zwighaft, Z., Reinke, H., & Asher, G. (2016) · Journal of Biological Rhythms · doi:10.1177/0748730416633552 · Cited by 29 · see citing works
Warming Up Your Tick-Tock: Temperature-Dependent Regulation of Circadian Clocks
Ki, Y., Ri, H., Lee, H., Yoo, E., Choe, J., & Lim, C. (2015) · The Neuroscientist · doi:10.1177/1073858415577083 · Cited by 24 · see citing works
Palm, D., Uzoni, A., Simon, F., Fischer, M., Coogan, A., Tucha, O., Thome, J., & Faltraco, F. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.06.007 · Cited by 20 · see citing works
Metabolism as an integral cog in the mammalian circadian clockwork
Gamble, K. L., & Young, M. E. (2013) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2013.786672 · Cited by 18 · see citing works
- Authors
- Kornmann, B., Schaad, O., Bujard, H., Takahashi, J. S., & Schibler, U.
- Affiliations
- University of Geneva (CH)
- Heidelberg University (DE)
- Northwestern University (US)
- Corresponding author
- Schibler, Ueli
- Venue
- PLoS Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2007-01-30
- Volume
- 5
- Issue
- 2
- Pages
- e34
- ISSN
- 1544-9173 (ISSN-L)
- 1545-7885
- PMC
- PMC1783671
- OpenAlex
- W2077404705
- Cited by
- 658
- References
- 52
- Citations by year
- 2026: 11 · 2025: 18 · 2024: 15 · 2023: 20 · 2022: 18 · 2021: 35 · 2020: 22 · 2019: 37 · 2018: 31 · 2017: 33 · 2016: 41 · 2015: 31 · 2014: 58 · 2013: 59 · 2012: 44
- FWCI
- 19.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
- Figshare (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- National Science Foundation
- Howard Hughes Medical Institute
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Bonizzi-Theler Stiftung
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Keywords
- circadian clock, peripheral oscillators, phase entrainment, NR1D1, Bmal1, mPer2, doxycycline-inducible expression, hepatic gene expression, circadian transcription, suprachiasmatic nucleus, clock synchronization
- MeSH terms
- Animals, Anti-Bacterial Agents, Biological Clocks, Chronobiology Phenomena, Circadian Rhythm, DNA-Binding Proteins, Doxycycline, Gene Expression Regulation, Liver, Male, Mice, Transgenic, Nuclear Proteins, Transcription Factors, Receptors, Cytoplasmic and Nuclear, Cell Cycle Proteins, Hepatocytes, Protein Array Analysis, Mice, Basic Helix-Loop-Helix Proteins, ARNTL Transcription Factors, Period Circadian Proteins, Nuclear Receptor Subfamily 1, Group D, Member 1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
