Clocks, metabolism, and the epigenome
Open accessAbstract
Many behaviors and physiological activities in living organisms display circadian rhythms, allowing the organisms to anticipate and prepare for the diurnal changes in the living environment. In this way, metabolic processes are aligned with the periodic environmental changes and behavioral cycles, such as the sleep/wake and fasting/feeding cycles. Disturbances of this alignment significantly increase the risk of metabolic diseases. Meanwhile, the circadian clock receives signals from the environment and feedback from metabolic pathways, and adjusts its activity and function. Growing evidence connects the circadian clock with epigenomic regulators. Here we review the recent advances in understanding the crosstalk between the circadian clock and energy metabolism through epigenomic programming and transcriptional regulation.
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Sleep is an emergent set of many physiologic processes under primarily neurobiological regulation that impact many physiologic systems.
“Sleep represents an emergent set of many physiologic processes under primarily neurobiological regulation that impact many physiologic systems.”
From Sleep, Health, and Society (2017) · cites this paper as [6]
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InfluentialCircadian Control of the NAD <sup>+</sup> Salvage Pathway by CLOCK-SIRT1
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InfluentialRegulation of circadian behaviour and metabolism by REV-ERB-α and REV-ERB-β
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A circadian rhythm orchestrated by histone deacetylase 3 controls hepatic lipid metabolism
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InfluentialRhythmic histone acetylation underlies transcription in the mammalian circadian clock
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Shift work and chronic disease: the epidemiological evidence
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InfluentialCryptochromes mediate rhythmic repression of the glucocorticoid receptor
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CLOCK-mediated acetylation of BMAL1 controls circadian function
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Insights from genomic profiling of transcription factors
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“Transcription factors control gene transcription by facilitating recruitment and activation of the transcription machinery, by altering the epigenome to recreate amore favorable environment for transcription, or most of the time by both (reviewed in Farnham, 2009).”
Circadian rhythms persist without transcription in a eukaryote
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“In picoeukaryotic algaOstreococcus tauri, oxidation of peroxiredoxin proteins undergoes circadian cycles independent of the transcriptional circadian clock of the alga (O’Neill et al., 2011).”
Rev-erbα and Rev-erbβ coordinately protect the circadian clock and normal metabolic functionPreprint
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“BMAL1 controls Ppara and Dbp, and REV-ERBa controls Shp and E4bp4 (Canaple et al., 2006; Duez et al., 2008).”
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 · cited 1× · 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).”
Rey, G., Cesbron, F., Rougemont, J., Reinke, H., Brunner, M., & Naef, F. (2011) · PLoS Biology · doi:10.1371/journal.pbio.1000595 · Cited by 473 · cited 2× · see citing works
“Both BMAL1/CLOCK and REV-ERBs display rhythmic genome binding and can drive the rhythmic expression of their targets (Ripperger and Schibler, 2006; Feng et al., 2011; Rey et al., 2011; Bugge et al., 2012).”
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“Insulin signaling leads to phosphorylation and inhibition of FOXO1, whose targets include stress response genes and gluconeogenic genes (Dong et al., 2008).”
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 · cited 3× · see citing works
“REV-ERBamay indirectly activate Cyp7a1 via E4BP4 and SHP, or via LXR (Duez et al., 2008; Le Martelot et al., 2009).”
NPAS2: A Gas-Responsive Transcription Factor
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“Heme is also a component of NPAS2, whose heterodimeric DNA binding with BMAL1 is inhibited by CO (Dioum et al., 2002; Gilles-Gonzalez and Gonzalez, 2004).”
Integration of microRNA miR-122 in hepatic circadian gene expressionPreprint
Gatfield, D., Martelot, G. L., Vejnar, C. E., Gerlach, D., Schaad, O., Fleury-Olela, F., Ruskeepää, A., Orešič, M., Esau, C., Zdobnov, E. M., et al. (2009) · Genes & Development · doi:10.1101/gad.1781009 · Cited by 389 · see citing works
A Molecular Mechanism for Circadian Clock Negative Feedback
Duong, H. A., Robles, M. S., Knutti, D., & Weitz, C. J. (2011) · Science · doi:10.1126/science.1196766 · Cited by 362 · cited 1× · see citing works
“Similarly, PER2 recruits SIN3A corepressor and HDAC1 through the polypyrimidine tract-binding protein-associated splicing factor (PSF) to the Per1 promoter (Duong et al., 2011).”
Schmutz, I., Ripperger, J. A., Baeriswyl-Aebischer, S., & Albrecht, U. (2010) · Genes & Development · doi:10.1101/gad.564110 · Cited by 361 · cited 1× · 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).”
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 · cited 1× · see citing works
“BMAL1 controls Ppara and Dbp, and REV-ERBa controls Shp and E4bp4 (Canaple et al., 2006; Duez et al., 2008).”
Shimba, S., Ogawa, T., Hitosugi, S., Ichihashi, Y., Nakadaira, Y., Kobayashi, M., Tezuka, M., Kosuge, Y., Ishige, K., Ito, Y., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025231 · Cited by 347 · cited 3× · see citing works
“Loss of BMAL1 increases circulating cholesterol, and loss of PER1/2 upregulates bile acid synthesis and results in hepatic cholestasis (Ma et al., 2009; Shimba et al., 2011).”
Reciprocal regulation of haem biosynthesis and the circadian clock in mammals
Kaasik, K., & Lee, C. C. (2004) · Nature · doi:10.1038/nature02724 · Cited by 341 · cited 1× · see citing works
“Heme inhibits BMAL1/NPAS2-activated ALAS1 expression and heme biosynthesis (Kaasik and Lee, 2004).”
Nader, N., Chrousos, G. P., & Kino, T. (2009) · The FASEB Journal · doi:10.1096/fj.08-117697 · Cited by 341 · cited 1× · see citing works
“CLOCK also acetylates GR, attenuates its DNA binding, and regulates glucocorticoid response (Nader et al., 2009; Charmandari et al., 2011).”
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 · cited 2× · see citing works
“NAD might play a role in regulating PARP-1 activity by feeding, but other mechanisms are also involved (Asher et al., 2010).”
Hepatic Hdac3 promotes gluconeogenesis by repressing lipid synthesis and sequestration
Sun, Z., Miller, R. A., Patel, R. T., Chen, J., Dhir, R., Wang, H., Zhang, D., Graham, M. J., Unterman, T. G., Shulman, G. I., et al. (2012) · Nature Medicine · doi:10.1038/nm.2744 · Cited by 335 · see citing works
Self-citationNuclear receptor corepressor and histone deacetylase 3 govern circadian metabolic physiology
Alenghat, T., Meyers, K. C., Mullican, S. E., Leitner, K., Adeniji‐Adele, A., Avila, J. L., Bućan, M., Ahima, R. S., Kaestner, K. H., & Lazar, M. A. (2008) · Nature · doi:10.1038/nature07541 · Cited by 293 · cited 1× · see citing works
“Indeed, evidence suggests that REV-ERBs might be responsible for circadian lipid biosynthesis in liver, which has been recognized for more than three decades (Hems et al., 1975; Alenghat et al., 2008; Feng et al., 2011).”
The histone methyltransferase MLL1 permits the oscillation of circadian gene expression
Katada, S., & Sassone‐Corsi, P. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1961 · Cited by 291 · cited 1× · see citing works
“MLL1 is required for circadian H3K4 methylation and H3 acetylation and for circadian gene expression (Katada and Sassone-Corsi, 2010).”
The relationship between nutrition and circadian rhythms in mammals
Froy, O. (2007) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2007.03.001 · Cited by 286 · cited 1× · see citing works
“Some of them are secreted in a circadian manner, including insulin and glucagon from pancreas, adiponectin and leptin from adipose, and ghrelin from stomach (reviewed in Froy, 2007).”
PERIOD1-Associated Proteins Modulate the Negative Limb of the Mammalian Circadian Oscillator
Brown, S. A., Ripperger, J. A., Kadener, S., Fleury-Olela, F., Vilbois, F., Rosbash, M., & Schibler, U. (2005) · Science · doi:10.1126/science.1107373 · Cited by 285 · cited 1× · see citing works
“PER1 associates with WD repeat-containing protein 5 (WDR5), and loss of WDR5 abolishes the circadian H3K4 and H3K9 methylation at the Rev-erba promoter (Brown et al., 2005).”
Calorie Restriction: Is AMPK a Key Sensor and Effector
Cantó, C., & Auwerx, J. (2011) · Physiology · doi:10.1152/physiol.00010.2011 · Cited by 282 · cited 5× · see citing works
“Sensing the nutritional/metabolic state through sirtuins and AMPK is a common theme, and also mediates responses to fasting and exercise (reviewed in Freyssenet, 2007; Cantó and Auwerx, 2011).”
InfluentialYin, L., & Lazar, M. A. (2005) · Molecular Endocrinology · doi:10.1210/me.2005-0057 · Cited by 274 · cited 1× · see citing works
“REV-ERBa recruits nuclear receptor corepressor (NCoR) and HDAC3 to deacetylate histones and repress transcription (Yin and Lazar, 2005).”
Glucocorticoid signaling synchronizes the liver circadian transcriptome
Reddy, A. B., Maywood, E. S., Karp, N. A., King, V. M., Inoue, Y., Gonzalez, F. J., Lilley, K. S., Kyriacou, C. P., & Hastings, M. H. (2007) · Hepatology · doi:10.1002/hep.21571 · Cited by 261 · cited 3× · see citing works
“In the absence of the central clock, daily glucocorticoid injection can restore about 60%of the liver circadian transcriptome, probably through hepatocyte nuclear factor 4a (HNF4a) (Maywood et al., 2007; Reddy et al., 2007).”
Um, J. H., Yang, S., Yamazaki, S., Kang, H., Viollet, B., Foretz, M., & Chung, J. H. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.c700070200 · Cited by 244 · cited 2× · see citing works
“Several studies place AMPK as a circadian clock regulator (Um et al., 2007, 2011; Vieira et al., 2008; Lamia et al., 2009) with two different mechanisms: AMPK activates CKIε and promotes PER2 degradation (Um et al., 2007), and AMPK phosphorylates CRY1 and destabilizes it (Lamia et al., 2009)…”
Histone Lysine Demethylase JARID1a Activates CLOCK-BMAL1 and Influences the Circadian Clock
DiTacchio, L., Le, H. D., Vollmers, C., Hatori, M., Witcher, M., Secombe, J., & Panda, S. (2011) · Science · doi:10.1126/science.1206022 · Cited by 244 · cited 1× · see citing works
“BMAL1/CLOCK also recruits JumonjiC and ARID domain-containing histone lysine demethylase 1a (JARID1a) to the Per2 promoter, though it appears that the circadian functions of JARID1a may be independent of its histone-modifying activity (DiTacchio et al., 2011).”
The clock gene Per2 links the circadian system to the estrogen receptor
Gery, S., Virk, R. K., Chumakov, K., Yu, A., & Koeffler, H. P. (2007) · Oncogene · doi:10.1038/sj.onc.1210585 · Cited by 218 · cited 1× · 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).”
Regulation of Bile Acid Synthesis by the Nuclear Receptor Rev-erbα
Duez, H., van der Veen, J. N., Duhem, C., Pourcet, B., Touvier, T., Fontaine, C., Derudas, B., Baugé, E., Havinga, R., Bloks, V. W., et al. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.05.035 · Cited by 212 · cited 3× · see citing works
“BMAL1 controls Ppara and Dbp, and REV-ERBa controls Shp and E4bp4 (Canaple et al., 2006; Duez et al., 2008).”
Naruse, Y., Oh‐hashi, K., Iijima, N., Naruse, M., Yoshioka, H., & Tanaka, M. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.14.6278-6287.2004 · Cited by 209 · cited 1× · see citing works
“Recently this mechanism was shown to be conserved in higher organisms, including human, at least in human red blood cells (O’Neill and Reddy, 2011).”
Histone Acetyltransferase-dependent Chromatin Remodeling and the Vascular Clock
Curtis, A. M., Seo, S., Westgate, E. J., Rudic, R. D., Smyth, E. M., Chakravarti, D., FitzGerald, G. A., & McNamara, P. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311973200 · Cited by 208 · see citing works
The N-CoR/Histone Deacetylase 3 Complex Is Required for Repression by Thyroid Hormone Receptor
Ishizuka, T., & Lazar, M. A. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.15.5122-5131.2003 · Cited by 202 · see citing works
HEMS, D. A., Rath, E. A., & Verrinder, T. R. (1975) · Biochemical Journal · doi:10.1042/bj1500167 · Cited by 198 · cited 1× · see citing works
“Indeed, evidence suggests that REV-ERBs might be responsible for circadian lipid biosynthesis in liver, which has been recognized for more than three decades (Hems et al., 1975; Alenghat et al., 2008; Feng et al., 2011).”
Jitrapakdee, S. (2011) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2011.10.001 · Cited by 189 · cited 1× · see citing works
“Pepck and G6Pase are activated by glucagon and fasting through cAMPresponsive binding element protein (CREB), repressed by insulin through the forkheadObox protein 1 (FOXO1), and stimulated by glucocorticoids through glucocorticoid receptor (GR) (reviewed in Jitrapakdee, 2012).”
The Polycomb Group Protein EZH2 Is Required for Mammalian Circadian Clock Function
Etchegaray, J., Yang, X., DeBruyne, J. P., Peters, A. H. F. M., Weaver, D. R., Jenuwein, T., & Reppert, S. M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m603722200 · Cited by 174 · cited 1× · see citing works
“BMAL1/CLOCK binds polycomb protein EZH2 and methylates H3K27 at the Per1 and Per2 promoters, which is essential for CRY-mediated transcriptional repression (Etchegaray et al., 2006).”
Signal transduction by heme-containing PAS-domain proteins
Gilles‐Gonzalez, M., & Gonzalez, G. (2004) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00941.2003 · Cited by 168 · see citing works
Absence of the SRC-2 Coactivator Results in a Glycogenopathy Resembling Von Gierke's Disease
Chopra, A. R., Louet, J., Saha, P., An, J., DeMayo, F. J., Xu, J., York, B., Karpen, S. J., Finegold, M. J., Moore, D. D., et al. (2008) · Science · doi:10.1126/science.1164847 · Cited by 161 · cited 4× · see citing works
“One study showed that RORs recruit the SWItch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex subunit BAF60a to drive rhythmic Bmal1 and G6Pase expression (Tao et al., 2011).”
InfluentialCalorie restriction and the exercise of chromatinPreprint
Vaquero, A., & Reinberg, D. (2009) · Genes & Development · doi:10.1101/gad.1807009 · Cited by 154 · cited 2× · see citing works
“CR is known to decrease blood insulin and thyroid hormone levels in human (reviewed in Vaquero and Reinberg, 2009).”
Circadian Dysregulation Disrupts Bile Acid Homeostasis
Ma, K., Xiao, R., Tseng, H.-T., Shan, L., Fu, L., & Moore, D. D. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006843 · Cited by 144 · cited 1× · see citing works
“Loss of BMAL1 increases circulating cholesterol, and loss of PER1/2 upregulates bile acid synthesis and results in hepatic cholestasis (Ma et al., 2009; Shimba et al., 2011).”
AMPK Regulates Circadian Rhythms in a Tissue- and Isoform-Specific Manner
Um, J.-H., Pendergast, J. S., Springer, D., Foretz, M., Viollet, B., Brown, A. L., Kim, M. K., Yamazaki, S., & Chung, J. H. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018450 · Cited by 140 · cited 1× · see citing works
“Several studies place AMPK as a circadian clock regulator (Um et al., 2007, 2011; Vieira et al., 2008; Lamia et al., 2009) with two different mechanisms: AMPK activates CKIε and promotes PER2 degradation (Um et al., 2007), and AMPK phosphorylates CRY1 and destabilizes it (Lamia et al., 2009)…”
Charmandari, E., Chrousos, G. P., Lambrou, G. I., Pavlaki, A., Koide, H., Ng, S. S. M., & Kino, T. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025612 · Cited by 139 · cited 1× · see citing works
“CLOCK also acetylates GR, attenuates its DNA binding, and regulates glucocorticoid response (Nader et al., 2009; Charmandari et al., 2011).”
The Structural Basis of Gas-Responsive Transcription by the Human Nuclear Hormone Receptor REV-ERBβ
Pardee, K., Xu, X., Reinking, J., Schuetz, A., Dong, A., Liu, S., Zhang, R., Tiefenbach, J., Lajoie, G., Plotnikov, A. N., et al. (2009) · PLoS Biology · doi:10.1371/journal.pbio.1000043 · Cited by 133 · cited 2× · see citing works
“Through heme, REV-ERBs can sense the redox state, and gases such as O2, NO, and CO, as they regulate REV-ERB structure and corepressor recruitment (Pardee et al., 2009).”
Tahara, Y., Otsuka, M., Fuse, Y., Hirao, A., & Shibata, S. (2011) · Journal of Biological Rhythms · doi:10.1177/0748730411405958 · Cited by 125 · cited 2× · see citing works
“Fasting and refeeding regulate the clock gene expression in peripheral tissues, particularly liver (Kawamoto et al., 2006; Tahara et al., 2011).”
Epigenomics in Environmental Health
Christensen, B. C., & Marsit, C. J. (2011) · Frontiers in Genetics · doi:10.3389/fgene.2011.00084 · Cited by 117 · cited 2× · see citing works
“Environmental factors such as nutrition, exercise, aging, and stress can signal through metabolic hormones, such as insulin and leptin, andmetabolites, such as nicotinamide adenine dinucleotide (NAD+), ADP, acetyl-CoA, and S-adenosylmethionine (SAM) (Christensen and Marsit, 2011).”
Negative feedback maintenance of heme homeostasis by its receptor, Rev-erbαPreprint
Wu, N., Yin, L., Hanniman, E. A., Joshi, S., & Lazar, M. A. (2009) · Genes & Development · doi:10.1101/gad.1825809 · Cited by 114 · cited 2× · see citing works
“In parallel, through REV-ERBa, heme represses PGC-1a transcription, a potent inducer of heme biosynthesis (Wu et al., 2009) Molecular Cell 47, July 27, 2012 ª2012 Elsevier Inc. 163 (Figure 3).”
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 · cited 1× · see citing works
“Rhythmic chromatin modification is not limited to the promoter of clock genes that have been studied, as ChIP-seq revealed that BMAL1 and REV-ERBs bind thousands of sites throughout the genome (Dufour et al., 2011; Feng et al., 2011; Rey et al., 2011; Bugge et al., 2012).”
Yin, L., Joshi, S., Wu, N., Tong, X., & Lazar, M. A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000438107 · Cited by 100 · cited 1× · see citing works
“Levels of the clock proteins are also subject to posttranslational regulation by casein kinases (CKIε and CKId) and ubiquitin E3 ligases b-TrCP, FBXL3, and ARF-BP1/PAM (Yin et al., 2010; reviewed in Bass and Takahashi, 2010).”
Transactivation mechanisms of mouse clock transcription factors, mClock and mArnt3
Takahata, S., Ozaki, T., Mimura, J., Kikuchi, Y., Sogawa, K., & Fujii‐Kuriyama, Y. (2000) · Genes to Cells · doi:10.1046/j.1365-2443.2000.00363.x · Cited by 97 · cited 1× · see citing works
“BMAL1 binds transcription coactivator p300 and possibly the CREB-binding protein (CBP), while CLOCK and NPAS2 bind p300 and the CBP-associated factor (PCAF) (Takahata et al., 2000; Etchegaray et al., 2003; Curtis et al., 2004).”
Gupta, N., & Ragsdale, S. W. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.193466 · Cited by 94 · cited 1× · see citing works
“Also, heme binding can be regulated by the redox state of the REV-ERBb protein (Gupta and Ragsdale, 2011).”
Energy sensing and regulation of gene expression in skeletal muscle
Freyssenet, D. G. (2006) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01126.2005 · Cited by 83 · cited 1× · see citing works
“Sensing the nutritional/metabolic state through sirtuins and AMPK is a common theme, and also mediates responses to fasting and exercise (reviewed in Freyssenet, 2007; Cantó and Auwerx, 2011).”
Relationship between AMPK and the transcriptional balance of clock-related genes in skeletal muscle
Vieira, E. C., Nilsson, E. C., Nerstedt, A., Ormestad, M., Long, Y. C., García-Rovés, P. M., Zierath, J. R., & Mahlapuu, M. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90510.2008 · Cited by 80 · see citing works
Altered behavioral and metabolic circadian rhythms in mice with disrupted NAD+ oscillation
Sahar, S., Nin, V., Barbosa, M. T., Chini, E. N., & Sassone-Corsi, P. (2011) · Aging · doi:10.18632/aging.100368 · Cited by 79 · cited 2× · see citing works
“Intracelluar NAD levels are circadian and are critical for circadian clock functions (Sahar et al., 2011).”
Phelan, C. A., Gampe, R. T., Lambert, M. H., Parks, D. J., Montana, V. G., Bynum, J. M., Timothy, B., Hu, X., Williams, S. P., Nolte, R. T., et al. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1860 · Cited by 78 · see citing works
Effects of Fasting and Re-Feeding on the Expression of Dec1, Per1, and Other Clock-Related Genes
Kawamoto, T., Noshiro, M., Furukawa, M., Honda, K. K., Nakashima, A., Ueshima, T., Usui, E., Katsura, Y., Fujimoto, K., Honma, S., et al. (2006) · The Journal of Biochemistry · doi:10.1093/jb/mvj165 · Cited by 73 · cited 1× · see citing works
“Fasting and refeeding regulate the clock gene expression in peripheral tissues, particularly liver (Kawamoto et al., 2006; Tahara et al., 2011).”
Daily oscillations in liver function: diurnal vs circadian rhythmicity
Davidson, A. J., Castañón‐Cervantes, O., & Stephan, F. K. (2004) · Liver International · doi:10.1111/j.1478-3231.2004.00917.x · Cited by 71 · cited 2× · see citing works
“The central clock is located in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus, while peripheral clocks are present in most organs, includingmetabolic organs such as liver, adipose, heart, muscle, and kidney (reviewed in Dibner et al., 2010).”
Genetic and Molecular Analysis of the Central and Peripheral Circadian Clockwork of MicePreprint
Maywood, E. S., O'Neill, J. S., Reddy, A. B., Chesham, J. E., Prosser, H. M., Kyriacou, C. P., Godinho, S. I. H., Nolan, P. M., & Hastings, M. H. (2007) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2007.72.005 · Cited by 63 · cited 1× · see citing works
“In the absence of the central clock, daily glucocorticoid injection can restore about 60%of the liver circadian transcriptome, probably through hepatocyte nuclear factor 4a (HNF4a) (Maywood et al., 2007; Reddy et al., 2007).”
The role of the orphan nuclear receptor Rev-Erbα in adipocyte differentiation and function
Laitinen, S., Fontaine, C., Fruchart, J., & Staels, B. (2005) · Biochimie · doi:10.1016/j.biochi.2004.12.006 · Cited by 55 · cited 1× · see citing works
“In addition, BMAL1 and REV-ERBa both regulate adipocyte differentiation (Laitinen et al., 2005; Shimba et al., 2005).”
Takeda, Y., Kang, H. S., Angers, M., & Jetten, A. M. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkq1335 · Cited by 48 · cited 1× · see citing works
“RORs interact with both corepressors and coactivators (reviewed in Jetten, 2009), and the rhythmic binding of RORs to the Npas2 promoter is positively correlated with DNA accessibility and histone acetylation (Takeda et al., 2011).”
Gimble, J. M., & Floyd, Z. E. (2009) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00090.2009 · Cited by 46 · cited 1× · see citing works
“Rhythmic activities were also observed in xenobiotic metabolism, glycogen metabolism, and amino acid metabolism, and in other metabolic tissues, such as fat (reviewed in Davidson et al., 2004; Gimble and Floyd, 2009).”
Tao, W., Chen, S., Shi, G., Guo, J., Xu, Y., & Liu, C. (2011) · Hepatology · doi:10.1002/hep.24514 · Cited by 40 · cited 3× · see citing works
“One study showed that RORs recruit the SWItch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex subunit BAF60a to drive rhythmic Bmal1 and G6Pase expression (Tao et al., 2011).”
The Circadian Change of Gluconeogenesis in the Liver
Kida, K., Nishio, T., Yokozawa, T., Nagai, K., Matsuda, H., & Nakagawa, H. (1980) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a133051 · Cited by 36 · cited 1× · see citing works
“For instance, gluconeogenesis peaks in the daytime with PEPCK activity (Kida et al., 1980).”
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Transcriptional architecture of the mammalian circadian clock
Takahashi, J. S. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.150 · Cited by 2,637 · see citing works
Thyroid Hormone Regulation of Metabolism
Mullur, R., Liu, Y.-Y., & Brent, G. A. (2014) · Physiological Reviews · doi:10.1152/physrev.00030.2013 · Cited by 2,421 · see citing works
“A central regulator of circadian rhythms, the RevErbA /RevErbA nuclear receptors, are activated by BMAL-1, which then suppresses BMAL-1 transcription (74).”
BackgroundTranscriptional 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
Time for food: the intimate interplay between nutrition, metabolism, and the circadian clock
Asher, G., & Sassone-Corsi, P. (2015) · Cell · doi:10.1016/j.cell.2015.03.015 · Cited by 844 · see citing works
Reprogramming of the Circadian Clock by Nutritional Challenge
Eckel‐Mahan, K. L., Patel, V. R., de Mateo, S., Orozco-Solís, R., Ceglia, N., Sahar, S., Dilag-Penilla, S. A., Dyar, K. A., Baldi, P., & Sassone‐Corsi, P. (2013) · Cell · doi:10.1016/j.cell.2013.11.034 · Cited by 711 · see citing works
Grandner, M. A. (2017) · Sleep Medicine Clinics · doi:10.1016/j.jsmc.2016.10.012 · Cited by 720 · see citing works
Circadian Clock NAD + Cycle Drives Mitochondrial Oxidative Metabolism in Mice
Peek, C. B., Affinati, A. H., Ramsey, K. M., Kuo, H.-Y., Yu, W., Sena, L. A., Ilkayeva, O., Marcheva, B., Kobayashi, Y., Omura, C., et al. (2013) · Science · doi:10.1126/science.1243417 · Cited by 658 · see citing works
Circadian Gene Bmal1 Regulates Diurnal Oscillations of Ly6C hi Inflammatory Monocytes
Nguyen, K. D., Fentress, S. J., Qiu, Y., Yun, K., Cox, J. S., & Chawla, A. (2013) · Science · doi:10.1126/science.1240636 · Cited by 647 · see citing works
Circadian Clock Proteins and Immunity
Curtis, A. M., Bellet, M. M., Sassone‐Corsi, P., & O'Neill, L. A. J. (2014) · Immunity · doi:10.1016/j.immuni.2014.02.002 · Cited by 644 · see citing works
“These areas have been reviewed extensively elsewhere (Aguilar-Arnal and SassoneCorsi, 2013; Bellet and Sassone-Corsi, 2010; Feng and Lazar, 2012).”
BackgroundMukherji, A., Kobiita, A., Ye, T., & Chambon, P. (2013) · Cell · doi:10.1016/j.cell.2013.04.020 · Cited by 560 · see citing works
Circadian Clocks and Feeding Time Regulate the Oscillations and Levels of Hepatic Triglycerides
Adamovich, Y., Rousso-Noori, L., Zwighaft, Z., Neufeld-Cohen, A., Golik, M., Kraut-Cohen, J., Wang, M., Han, X., & Asher, G. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2013.12.016 · Cited by 410 · see citing works
Mauvoisin, D., Wang, J., Jouffe, C., Martin, E., Atger, F., Waridel, P., Quadroni, M., Gachon, F., & Naef, F. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1314066111 · Cited by 329 · see citing works
“In mammals, the molecular oscillator uses interconnected transcriptional and translational feedback loops, in which multiple layers of control, including temporal posttranscriptional and posttranslational regulation, play important roles (3).”
BackgroundThe intestinal microbiota programs diurnal rhythms in host metabolism through histone deacetylase 3
Kuang, Z., Wang, Y., Li, Y., Ye, C., Ruhn, K. A., Behrendt, C. L., Olson, E. N., & Hooper, L. V. (2019) · Science · doi:10.1126/science.aaw3134 · Cited by 330 · see citing works
“A key mechanism by which the circadian clock generates rhythms in metabolic gene expression is by regulating the recruitment of histone modifiers to chromatin (10-13).”
BackgroundDiscrete functions of nuclear receptor Rev-erbα couple metabolism to the clock
Zhang, Y., Fang, B., Emmett, M. J., Damle, M., Sun, Z., Feng, D., Armour, S. M., Remsberg, J. R., Jager, J., Soccio, R. E., et al. (2015) · Science · doi:10.1126/science.aab3021 · Cited by 321 · see citing works
Ruben, M. D., Wu, G., Smith, D. F., Schmidt, R. E., Francey, L. J., Lee, Y. Y., Anafi, R. C., & Hogenesch, J. B. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aat8806 · Cited by 314 · see citing works
Partitioning Circadian Transcription by SIRT6 Leads to Segregated Control of Cellular Metabolism
Masri, S., Rigor, P., Cervantes, M., Ceglia, N., Sebastian, C., Xiao, C., Roqueta-Rivera, M., Deng, C., Osborne, T. F., Mostoslavsky, R., et al. (2014) · Cell · doi:10.1016/j.cell.2014.06.050 · Cited by 292 · see citing works
Rhythmic Oxygen Levels Reset Circadian Clocks through HIF1α
Adamovich, Y., Ladeuix, B., Golik, M., Koeners, M. P., & Asher, G. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.09.014 · Cited by 283 · see citing works
“The molecular makeup for circadian rhythm generation is based on interlocked negative transcription-translation feedback loops (Feng and Lazar, 2012; Partch et al., 2014).”
BackgroundThe nuclear receptor Rev-erbα controls circadian thermogenic plasticity
Gerhart‐Hines, Z., Feng, D., Emmett, M. J., Everett, L. J., Loro, E., Briggs, E. R., Bugge, A. K., Hou, C., Ferrara, C., Seale, P., et al. (2013) · Nature · doi:10.1038/nature12642 · Cited by 261 · see citing works
CLOCK:BMAL1 is a pioneer-like transcription factorPreprint
Menet, J. S., Pescatore, S., & Rosbash, M. (2014) · Genes & Development · doi:10.1101/gad.228536.113 · Cited by 252 · see citing works
Sullivan, M. R., Mattaini, K. R., Dennstedt, E. A., Nguyen, A. A., Sivanand, S., Reilly, M. F., Meeth, K. M., Muir, A., Darnell, A. M., Bosenberg, M., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.02.015 · Cited by 242 · see citing works
“Thus, fluctuations in plasma serine levels between meals, in addition to circadian effects on metabolic gene expression affecting nutrient levels in blood (Feng and Lazar, 2012), could lower serine in some tissues to levels where PHGDH expression might provide an advantage for proliferation.”
BackgroundThe circadian clock and liver function in health and disease
Mukherji, A., Bailey, S. M., Staels, B., & Baumert, T. F. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2019.03.020 · Cited by 246 · see citing works
Ruben, M. D., Smith, D. F., FitzGerald, G. A., & Hogenesch, J. B. (2019) · Science · doi:10.1126/science.aax7621 · Cited by 239 · see citing works
Hooda, J., Shah, A. N., & Li, Z. (2014) · Nutrients · doi:10.3390/nu6031080 · Cited by 211 · see citing works
“Circadian rhythm is the clock governing many important behaviors and physiological processes in humans, such as sleep/wake cycle, feeding, body temperature, hormone secretion, and metabolism [109].”
Backgroundvel Szic, K. S., Declerck, K., Vidaković, M., & Vanden Berghe, W. (2015) · Clinical Epigenetics · doi:10.1186/s13148-015-0068-2 · Cited by 192 · see citing works
“dehydrogenase kinase; AKT/PKB, protein kinase B; PGC1, peroxisome proliferat metabolism, cellular signaling, and the epigenetic control of transcription programs [108-116] (Figure 3).”
BackgroundJakubowicz, D., Wainstein, J., Landau, Z., Raz, I., Ahren, B., Chapnik, N., Ganz, T., Menaged, M., Barnea, M., Bar-Dayan, Y., et al. (2017) · Diabetes Care · doi:10.2337/dc16-2753 · Cited by 178 · see citing works
“, regulation of hepatic gluconeogenesis and pancreatic b-cell insulin secretion (7).”
BackgroundGrandner, M. A. (2022) · Sleep Medicine Clinics · doi:10.1016/j.jsmc.2022.03.001 · Cited by 179 · 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
Fawad, J. A., Luzader, D., Hanson, G. F., Moutinho, T. J., McKinney, C. A., Mitchell, P., Brown-Steinke, K., Kumar, A., Park, M., Lee, S., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2022.07.051 · Cited by 167 · see citing works
Circadian Clock Control by Polyamine Levels through a Mechanism that Declines with Age
Zwighaft, Z., Aviram, R., Shalev, M., Rousso-Noori, L., Kraut‐Cohen, J., Golik, M., Brandis, A. S., Reinke, H., Aharoni, A., Kahana, C., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.09.011 · Cited by 159 · see citing works
“The coordinated activity of these feedback loops drives cyclic gene expression with an 24 hr period, both in cultured cells and living animals (Feng and Lazar, 2012; Mohawk et al., 2012).”
BackgroundHepatic mTORC1 controls locomotor activity, body temperature, and lipid metabolism through FGF21
Cornu, M., Oppliger, W., Albert, V., Robitaille, A. M., Trapani, F., Quagliata, L., Fuhrer, T., Sauer, U., Terracciano, L., & Hall, M. N. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1412047111 · Cited by 148 · see citing works
“Core clock components, in addition to FGF21, are also key regulators of locomotor activity, body temperature, and hepatic glucose and lipid metabolism (40, 41).”
BackgroundRegulation of Circadian Clocks by Redox Homeostasis
Stangherlin, A., & Reddy, A. B. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.r113.457564 · Cited by 152 · see citing works
“This classical model based on transcription has been slightly revisited in light of new data showing that proteosomal degradation, epigenetic modulation of gene expression and post-translational modifications of mRNA play key roles in generating molecular rhythmicity (11, 14-16).”
BackgroundRas-Mediated Deregulation of the Circadian Clock in Cancer
Relógio, A., Thomas, P. E., Medina-Pérez, P., Reischl, S., Bervoets, S., Gloc, E., Riemer, P., Mang‐Fatehi, S., Maier, B., Schäfer, R., et al. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004338 · Cited by 146 · see citing works
“A link between the circadian clock, energy metabolism and epigenetic (re)programming has been established earlier [67–69].”
BackgroundAviram, R., Manella, G., Kopelman, N. M., Neufeld-Cohen, A., Zwighaft, Z., Elimelech, M., Adamovich, Y., Golik, M., Wang, C., Han, X., et al. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.04.002 · Cited by 143 · see citing works
“Circadian clocks regulate lipid homeostasis, and disruption of circadian rhythmicity is associated with obesity and metabolic syndrome (Adamovich et al., 2015; Bass, 2012; Feng and Lazar, 2012).”
BackgroundThe 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
“In addition to the ‘‘secondary’’ REV-ERB/ROR loop, other loops contributing to clock function link the clock to metabolism (Asher and Schibler, 2011; Feng and Lazar, 2012).”
Grandner, M. A. (2020) · Sleep Medicine Clinics · doi:10.1016/j.jsmc.2020.02.017 · Cited by 139 · see citing works
Metabolic control through glucocorticoid hormones: An update
Rose, A. J., & Herzig, S. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.03.007 · Cited by 134 · see citing works
Circadian clocks, epigenetics, and cancer
Masri, S., Kinouchi, K., & Sassone‐Corsi, P. (2014) · Current Opinion in Oncology · doi:10.1097/cco.0000000000000153 · Cited by 133 · see citing works
“The circadian clock is an endogenous, self-sustaining pacemaker that operates with a periodicity of 24 h, in order to maintain proper rhythms in sleep– wake cycles, behavior, metabolism, hormone secretion, and cell cycle [1,2].”
BackgroundRibas‐Latre, A., & Eckel‐Mahan, K. L. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2015.12.006 · Cited by 133 · see citing works
“These important nuclear receptors both compete for a binding site within the response element (RORE) into the Bmal1 promoter, generating another loop of regulation [42].”
BackgroundInfluentialNuclear metabolism and the regulation of the epigenome
Boon, R., da Silveira, G. G., & Mostoslavsky, R. (2020) · Nature Metabolism · doi:10.1038/s42255-020-00285-4 · Cited by 125 · see citing works
Cycles in spatial and temporal chromosomal organization driven by the circadian clock
Aguilar‐Arnal, L., Hakim, O., Patel, V. R., Baldi, P., Hager, G. L., & Sassone‐Corsi, P. (2013) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2667 · Cited by 125 · see citing works
The Role of Sirt6 in Obesity and Diabetes
Kuang, J., Chen, L., Tang, Q., Zhang, J., Li, Y., & He, J. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00135 · Cited by 122 · see citing works
“The clock has a central role in the circadian rhythm (Feng and Lazar, 2012).”
BackgroundNAD(+)-SIRT1 control of H3K4 trimethylation through circadian deacetylation of MLL1
Aguilar-Arnal, L., Katada, S., Orozco-Solis, R., & Sassone-Corsi, P. (2015) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2990 · Cited by 117 · see citing works
“Thereby, our findings provide an additional paradigm by which metabolism and chromatin remodeling act in concert to keep adequate homeostasis 1,2 .”
Borengasser, S. J., Kang, P., Faske, J. B., Gómez-Acevedo, H., Blackburn, M. L., Badger, T. M., & Shankar, K. (2014) · PLoS ONE · doi:10.1371/journal.pone.0084209 · Cited by 112 · see citing works
“or amplitude of core clock components are associated with the development of metabolic diseases, including obesity, diabetes, and cardiovascular dysfunction [37,60].”
BackgroundA Pilot Characterization of the Human Chronobiome
Skarke, C., Lahens, N. F., Rhoades, S. D., Campbell, A. E., Bittinger, K. L., Bailey, A., Hoffmann, C., Olson, R. S., Chen, L., Yang, G., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-17362-6 · Cited by 111 · see citing works
The genetics of insomnia – Evidence for epigenetic mechanisms?
Palagini, L., Biber, K. P. H., & Riemann, D. W. (2013) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2013.05.002 · Cited by 113 · see citing works
Al‐Nuaimi, Y., Hardman, J. A., Bı́ró, T., Haslam, I. S., Philpott, M. P., Tóth, B. I., Farjo, N. P., FARJO, B. K., Baier, G., Watson, R. E. B., et al. (2013) · Journal of Investigative Dermatology · doi:10.1038/jid.2013.366 · Cited by 110 · see citing works
The orphan nuclear receptors at their 25-year reunion
Mullican, S. E., DiSpirito, J. R., & Lazar, M. A. (2013) · Journal of Molecular Endocrinology · doi:10.1530/jme-13-0212 · Cited by 102 · see citing works
“For example, Rev-erb expression inmost tissues is circadian and is tightly controlled by the core circadian clock TFs, BMAL1 and CLOCK, as well as repressing its own transcription (Feng & Lazar 2012).”
Cui, M., Zheng, M., Sun, B., Wang, Y., Ye, L., & Zhang, X. (2015) · Neoplasia · doi:10.1016/j.neo.2014.11.004 · Cited by 97 · see citing works
Schupp, M., Chen, F., Briggs, E. R., Rao, S. J., Pelzmann, H. J., Pessentheiner, A. R., Bogner‐Strauß, J. G., Lazar, M. A., Baldwin, D. A., & Prokesch, A. (2013) · BMC Genomics · doi:10.1186/1471-2164-14-758 · Cited by 96 · see citing works
“Per1 is an essential regulator in the core clock machinery of circadian rhythm [10,68] and, in LIV and AT at the beginning of the light phase, it was previously shown that its expression is higher in fasting compared to control fed mice [69,70].”
BackgroundSiersbæk, M. S., Varticovski, L., Yang, S., Baek, S., Nielsen, R., Mandrup, S., Hager, G. L., Chung, J. H., & Grøntved, L. (2017) · Scientific Reports · doi:10.1038/srep40220 · Cited by 96 · see citing works
PPARs and Mitochondrial Metabolism: From NAFLD to HCC
Mello, T., Materozzi, M., & Galli, A. (2016) · PPAR Research · doi:10.1155/2016/7403230 · Cited by 92 · see citing works
Tain, Y., Lin, Y., Sheen, J.-M., Yu, H., Tiao, M., Chen, C.-C., Tsai, C., Huang, L., & Hsu, C. (2017) · Nutrients · doi:10.3390/nu9040357 · Cited by 91 · see citing works
“In agreement with previous studies showing that HF diets alter circadian clock function [13,49], we observed that maternal HF diet upregulated mRNA expression of the positive element (Baml) and negative elements (Cry1 and Per2) in females.”
BackgroundResultThe Circadian Clock Regulates Adipogenesis by a Per3 Crosstalk Pathway to Klf15
Aggarwal, A., Costa, M. J. D. C., Rivero‐Gutiérrez, B., Ji, L., Morgan, S. L., & Feldman, B. J. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.11.004 · Cited by 89 · see citing works
“Peripheral circadian clocks have a significant influence over systemic metabolism (reviewed in (Asher and Schibler, 2011; Bass and Takahashi, 2010; Feng and Lazar, 2012)).”
BackgroundGlucocorticoid hormones and energy homeostasis
de Guia, R. M., Rose, A. J., & Herzig, S. (2014) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2014-0021 · Cited by 85 · see citing works
Chromatin landscape and circadian dynamics: Spatial and temporal organization of clock transcription
Aguilar‐Arnal, L., & Sassone‐Corsi, P. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1411264111 · Cited by 83 · see citing works
“Metabolism and chromatin remodeling intersect at the level of specific metabolic cofactors that enzymes need to catalyze reactions (21, 87, 88).”
BackgroundChronotherapy: Intuitive, Sound, Founded…But Not Broadly Applied
Selfridge, J. M., Gotoh, T., Schiffhauer, S., Liu, J., Stauffer, P. E., Li, A., Capelluto, D. G. S., & Finkielstein, C. V. (2016) · Drugs · doi:10.1007/s40265-016-0646-4 · Cited by 84 · see citing works
The Circadian Nature of Mitochondrial Biology
Manella, G., & Asher, G. (2016) · Frontiers in Endocrinology · doi:10.3389/fendo.2016.00162 · Cited by 81 · see citing works
Perrino, C., Ferdinandy, P., Bøtker, H. E., Brundel, B. J. J. M., Collins, P. D., Davidson, S. M., den Ruijter, H. M., Engel, F. B., Gerdts, E., Girão, H., et al. (2020) · Cardiovascular Research · doi:10.1093/cvr/cvaa155 · Cited by 84 · see citing works
CLOCK Acetylates ASS1 to Drive Circadian Rhythm of Ureagenesis
Lin, R., Mo, Y., Zha, H., Qu, Z., Xie, P., Zhu, Z., Xu, Y., Xiong, Y., & Guan, K. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.09.008 · Cited by 80 · see citing works
The hepatic circadian clock fine-tunes the lipogenic response to feeding through RORα/γPreprint
Zhang, Y., Papazyan, R., Damle, M., Fang, B., Jager, J., Feng, D., Peed, L. C., Guan, D., Sun, Z., & Lazar, M. A. (2017) · Genes & Development · doi:10.1101/gad.302323.117 · Cited by 76 · see citing works
“The autonomous rhythm of hepatocytes is entrained by not only the hormonal and neuronal signals from the master clock but also the nutrients and metabolites whose oscillation is in large part determined by feeding activity (Kornmann et al. 2007; Feng and Lazar 2012).”
BackgroundZhu, B., Gates, L. A., Stashi, E., Dasgupta, S., Gonzales, N., Dean, A., Dacso, C. C., York, B., & O’Malley, B. W. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.10.024 · Cited by 75 · see citing works
“GO analysis revealed that only ROR target genes containing ROR/SRC-2/BAF180 overlapping peaks are enriched in fatty acid and steroid metabolic pathways (Table S3), most of which are under circadian regulation (Asher and Schibler, 2011; Feng and Lazar, 2012).”
BackgroundCircadian Control of Inflammatory Processes in Atherosclerosis and Its Complications
Steffens, S., Winter, C., Schloss, M. J., Hidalgo, A., Weber, C., & Soehnlein, O. (2017) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.117.309374 · Cited by 75 · see citing works
Endothelial MRTF-A mediates angiotensin II induced cardiac hypertrophy
Weng, X., Yu, L., Peng, L., Chen, D., Cheng, X. F., Yang, Y., Li, L., Zhang, T., Zhou, B., Wu, X., et al. (2014) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2014.11.009 · Cited by 74 · see citing works
“The concerted effort to decipher the human epigenome has engendered critical breakthroughs for such complex human pathologies as cancer and metabolic syndrome [47,48].”
BackgroundTMEM14C is required for erythroid mitochondrial heme metabolism
Yien, Y. Y., Robledo, R. F., Schultz, I. J., Takahashi‐Makise, N., Gwynn, B., Bauer, D. E., Dass, A., Yi, G., Li, L., Hildick-Smith, G. J., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci76979 · Cited by 71 · see citing works
Domingues, R. G., & Hepworth, M. R. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00116 · Cited by 68 · see citing works
Visualizing the Architectures and Interactions of Nuclear Receptors
Khorasanizadeh, S., & Rastinejad, F. (2016) · Endocrinology · doi:10.1210/en.2016-1559 · Cited by 64 · see citing works
Circadian rhythms and environmental disturbances – underexplored interactions
Prokkola, J. M., & Nikinmaa, M. (2018) · Journal of Experimental Biology · doi:10.1242/jeb.179267 · Cited by 64 · see citing works
“Although the basic generation of circadian rhythms involves the rhythmic transcription of genes in the positive- and negativefeedback loops, fine-tuning of the rhythms occurs by many posttranscriptional and epigenetic mechanisms (Alvarez-Saavedra et al., 2011; Beckwith and Yanovsky, 2014; Feng and Lazar, 2012; Lee et…”
BackgroundKalviša, A., Siersbæk, M. S., Præstholm, S. M., Christensen, L. J. L., Nielsen, R., Stöhr, O., Vettorazzi, S., Tuckermann, J. P., White, M. F., Mandrup, S., et al. (2018) · PLoS Biology · doi:10.1371/journal.pbio.2006249 · Cited by 64 · see citing works
Circadian Clock–Controlled Drug Metabolism: Implications for Chronotherapeutics
Lu, D., Zhao, M., Chen, M., & Wu, B. (2020) · Drug Metabolism and Disposition · doi:10.1124/dmd.120.090472 · Cited by 64 · see citing works
“…system that generates and regulates circadian rhythms in physiological, cellular, and biochemical processes, as well as in behaviors, such as body temperature, cell metabolism, hormone release, and sleep-wake cycle in mammals ((Paschos et al., 2010) Feng and Lazar, 2012; (Thaiss et al., 2015)).”
BackgroundRegulation of Heme Synthesis by Mitochondrial Homeostasis Proteins
Yien, Y. Y., & Perfetto, M. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.895521 · Cited by 63 · see citing works
“…proteins that regulate a diverse range life-essential redox processes such as oxygen transport, respiration, detoxification, gas sensing, circadian rhythm and control of gene expression (Chen and Paw, 2012; Feng and Lazar, 2012; Girvan and Munro, 2013; Shimizu et al., 2015; Shimizu et al., 2019).”
BackgroundValenzuela, F. J., Vera, J., Venegas, C., Muñoz, S., Oyarce, S., Muñoz, K., & Lagunas, C. (2016) · International Journal of Endocrinology · doi:10.1155/2016/2746909 · Cited by 61 · see citing works
“Themolecular clock is organized by transcriptional/translational feedback loop of clock genes named Clock, Bmal1, Per1–3, and Cry1-2.”
BackgroundNorth, M. L., Jones, M. J., MacIsaac, J. L., Morin, A. M., Steacy, L. M., Gregor, A., Kobor, M. S., & Ellis, A. K. (2017) · Allergy · doi:10.1111/all.13263 · Cited by 61 · see citing works
“A strength of this study was the inclusion of nonallergic individuals, which ensured that the DNA methylation changes we identified were allergy-specific, and controlled by controlling for the “whitecoat effect” as well as diurnal variation.(43) However, the number of nonallergic participants was smaller than the alle…”
BackgroundConnecting cellular metabolism to circadian clocks
Rey, G., & Reddy, A. B. (2013) · Trends in Cell Biology · doi:10.1016/j.tcb.2013.01.003 · Cited by 60 · see citing works
Emerging Insight Into the Role of Circadian Clock Gene BMAL1 in Cellular Senescence
Zhang, W., Xiong, Y., Tao, R., Panayi, A. C., Mi, B., & Liu, G. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.915139 · Cited by 59 · see citing works
Kim, H., Zheng, Z., Walker, P. D., Kapatos, G., & Zhang, K. (2017) · Molecular and Cellular Biology · doi:10.1128/mcb.00048-17 · Cited by 57 · see citing works
“Previous work has demonstrated the intimate and reciprocal interaction between the circadian clock system and fundamental metabolic pathways in the liver (1, 5).”
BackgroundCircadian clock genes as promising therapeutic targets for autoimmune diseases
Xiang, K., Xu, Z., Hu, Y., He, Y.-S., Wu, G., Li, T., Wang, X., Ding, L., Zhang, Q., Tao, S., et al. (2021) · Autoimmunity Reviews · doi:10.1016/j.autrev.2021.102866 · Cited by 57 · see citing works
Saino, N., Ambrosini, R., Albetti, B., Caprioli, M., Giorgio, B. D., Gatti, E., Liechti, F., Parolini, M., Romanò, A., Romano, M., et al. (2017) · Scientific Reports · doi:10.1038/srep45412 · Cited by 56 · see citing works
Global approaches for telling time: Omics and the Arabidopsis circadian clock
Chow, B. Y., & Kay, S. A. (2013) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2013.02.005 · Cited by 52 · see citing works
Genome-wide circadian rhythm detection methods: systematic evaluations and practical guidelines
Mei, W., Jiang, Z., Chen, Y., Chen, L., Sancar, A., & Jiang, Y. (2020) · Briefings in Bioinformatics · doi:10.1093/bib/bbaa135 · Cited by 53 · see citing works
Ma, X., Zhou, Z., Chen, Y., Wu, Y., & Liu, Y. (2015) · Diabetologia · doi:10.1007/s00125-015-3807-1 · Cited by 51 · see citing works
Sengupta, S., Yang, G., O’Donnell, J. C., Hinson, M. D., McCormack, S. E., Falk, M. J., La, P., Robinson, M. B., Williams, M., Yohannes, M. T., et al. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.02.004 · Cited by 50 · see citing works
“These genes control many vital cellular functions such as the redox state (10-13), metabolism and proliferation (14, 15), with approximately 10-20% of the transcriptome thought to be under circadian control (16, 17).”
BackgroundDexras1 mediates glucocorticoid-associated adipogenesis and diet-induced obesity
Cha, J. Y., Kim, H. J., Yu, J. H., Xu, J., Kim, D., Paul, B. D., Choi, H., Kim, S., Lee, Y. J., Ho, G. P. H., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1320454110 · Cited by 49 · see citing works
Takeda, T., Mu, A., Tai, T. T., Kitajima, S., & Taketani, S. (2015) · Scientific Reports · doi:10.1038/srep10488 · Cited by 49 · see citing works
Perturbation of the circadian clock and pathogenesis of NAFLD
Mukherji, A., Dachraoui, M., & Baumert, T. F. (2020) · Metabolism · doi:10.1016/j.metabol.2020.154337 · Cited by 50 · see citing works
Weger, M., Weger, B. D., Diotel, N., Rastegar, S., Hirota, T., Kay, S. A., Strähle, U., & Dickmeis, T. (2013) · Developmental Biology · doi:10.1016/j.ydbio.2013.04.035 · Cited by 48 · see citing works
CircadiOmics: circadian omic web portal
Ceglia, N., Liu, Y., Chen, S., Agostinelli, F., Eckel‐Mahan, K. L., Sassone‐Corsi, P., & Baldi, P. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky441 · Cited by 49 · see citing works
Circadian Genomics Reveal a Role for Post-transcriptional Regulation in Mammals
Kojima, S., & Green, C. B. (2014) · Biochemistry · doi:10.1021/bi500707c · Cited by 47 · see citing works
Cancer cell metabolism connects epigenetic modifications to transcriptional regulation
Morrison, A. J. (2021) · FEBS Journal · doi:10.1111/febs.16032 · Cited by 46 · see citing works
Photoreceptor phagocytosis is mediated by phosphoinositide signaling
Mustafi, D., Kevany, B. M., Genoud, C., Bai, X., & Palczewski, K. (2013) · The FASEB Journal · doi:10.1096/fj.13-237537 · Cited by 44 · see citing works
Chen, J.-H., Lu, L. W., Ge, Q., Feng, D., Yu, J., Liu, B., Zhang, R., Zhang, X., Ouyang, C., & Chen, F. (2023) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2021.1974335 · Cited by 45 · see citing works
“Further into investigating the mammalian circadian clock, it is discovered that the circadian regulation of most of the hormones and enzymes taking part in metabolism and energy homeostasis in peripheral tissues is mediated by CLOCK:BMAL1 heterodimer (Froy 2010; Feng and Lazar 2012).”
BackgroundSelf-citationDeleted in breast cancer-1 (DBC-1) in the interface between metabolism, aging and cancer
Chini, E. N., Chini, C. C. S., Nin, V., & Escande, C. (2013) · Bioscience Reports · doi:10.1042/bsr20130062 · Cited by 45 · see citing works
Yien, Y. Y., Shi, J., Chen, C., Cheung, J., Grillo, A. S., Shrestha, R., Li, L., Zhang, X., Kafina, M. D., Kingsley, P. D., et al. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.002742 · Cited by 44 · see citing works
Ghrelin Restores the Disruption of the Circadian Clock in Steatotic Liver
Wang, Q., Yin, Y., & Zhang, W. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19103134 · Cited by 42 · see citing works
“At the molecular level, circadian oscillations are determined by a transcriptional autoregulatory feedback loop in which Bmal1, Clock, NPAS2, and ROR proteins act as transcriptional activators, while Per, Cry, and Rev-erb function as inhibitors to produce 24 h self-sustained rhythmic transcription of their own and tar…”
BackgroundHistone Modification Patterns and Their Responses to Environment
Dai, H., & Wang, Z. (2014) · Current Environmental Health Reports · doi:10.1007/s40572-013-0008-2 · Cited by 41 · see citing works
Transcription mediated insulation and interference direct gene cluster expression switches
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The regulation of circadian clock by tumor necrosis factor alpha
Ertosun, M. G., Koçak, G., & Özeş, O. N. (2019) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2019.04.001 · Cited by 40 · see citing works
MRG15 orchestrates rhythmic epigenomic remodelling and controls hepatic lipid metabolism
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Sexual Dimorphism in Circadian Physiology Is Altered in LXRα Deficient Mice
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“In addition to these transcriptional mechanisms, the circadian molecular network is also extensively regulated post-translationally [7–9] as well as through chromatin remodelling [10, 11].”
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- Authors
- Feng, D., & Lazar, M. A.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Lazar, Mitchell A.
- ORCID
- Lazar, Mitchell A.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2012-07
- Volume
- 47
- Issue
- 2
- Pages
- 158-167
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC3408602
- OpenAlex
- W2016922540
- Cited by
- 271
- References
- 107
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 8 · 2023: 7 · 2022: 18 · 2021: 18 · 2020: 26 · 2019: 13 · 2018: 28 · 2017: 18 · 2016: 19 · 2015: 31 · 2014: 29 · 2013: 39 · 2012: 1
- FWCI
- 3.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK43806, R01DK045586, DK 45586, RC1DK086239, R37DK043806, R01DK043806)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Keywords
- circadian clock, circadian rhythm, energy metabolism, epigenome, transcriptional regulation, metabolic disorders, sleep-wake cycle
- MeSH terms
- Animals, Cell Nucleus, Circadian Rhythm, Cytoplasm, Gene Expression Regulation, Glucose, Heme, Histones, Homeostasis, Humans, Lipids, Liver, Models, Biological, Risk, Transcription, Genetic, Epigenomics
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