The DOI matches its Crossref record; 64 of the 64 references it cites were found in a registry or an index.
The mammalian clock component PERIOD2 coordinates circadian output by interaction with nuclear receptors
Open accessAbstract
Mammalian circadian clocks provide a temporal framework to synchronize biological functions. To obtain robust rhythms with a periodicity of about a day, these clocks use molecular oscillators consisting of two interlocked feedback loops. The core loop generates rhythms by transcriptional repression via the Period (PER) and Cryptochrome (CRY) proteins, whereas the stabilizing loop establishes roughly antiphasic rhythms via nuclear receptors. Nuclear receptors also govern many pathways that affect metabolism and physiology. Here we show that the core loop component PER2 can coordinate circadian output with the circadian oscillator. PER2 interacts with nuclear receptors including PPARalpha and REV-ERBalpha and serves as a coregulator of nuclear receptor-mediated transcription. Consequently, PER2 is rhythmically bound at the promoters of nuclear receptor target genes in vivo. In this way, the circadian oscillator can modulate the expression of nuclear receptor target genes like Bmal1, Hnf1alpha, and Glucose-6-phosphatase. The concept that PER2 may propagate clock information to metabolic pathways via nuclear receptors adds an important facet to the clock-dependent regulation of biological networks.
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“Per2 mutant mice show reduced fasting glycemia, a loss of rhythmic glycogen accumulation in the liver, elevated plasma insulin levels and impaired gluconeogenesis [20–22]”
From Circadian control of glucose metabolism (2014) · cites this paper as [20]
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Items 301–358 of 358
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Nutrient Abundance Signals the Changing of the Seasons by Phosphorylating PER2Preprint
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BackgroundSleep deprivation exacerbates experimental colitis via down-regulating the clock gene Per2
Jiang, X., Wu, P., Chen, H., Cui, J., Lv, X., Ha, L., Wu, M., Chen, M., Wu, B., Xu, H., et al. (2025) · Biochemical Pharmacology · doi:10.1016/j.bcp.2025.117224 · Cited by 1
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Mutually exclusive alternative pre-mRNA splicing promotes adaptive metabolic stress signaling by JNK
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“(c) Thirdly, PER2 has recently been shown to propagate clock information to metabolic genes by directly interacting with and acting as a co-regulator of nuclear receptor-mediated transcription [44].”
BackgroundCell signaling, receptors, electrical effects and therapy in circadian rhythm
Kovacic, P., & Somanathan, R. (2013) · Journal of Receptors and Signal Transduction · doi:10.3109/10799893.2013.822890 · Cited by 1
“Mammalian circadian clock provides a temporal framework to synchronize biological functions (43).”
BackgroundCircadian Rhythms and Metabolism
Grosbellet, E., & Challet, É. (2016) · Springer eBooks · doi:10.1007/978-3-319-11251-0_32 · Cited by 1
Circadian Rhythms and Exercise Metabolism
Wolff, C. A., Hesketh, S. J., & Esser, K. A. (2022) · Physiology in health and disease · doi:10.1007/978-3-030-94305-9_16 · Cited by 1
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TRPV1 Desensitization Abolishes Metabolic Effects of Time-Restricted Feeding in Rats
Horta, N. A. C., Cardoso, T. S. R., Fernandes, P., Araújo, F. M., Luciano, P. L. C., Drummond, L. R., Coimbra, C. C., & Poletini, M. O. (2025) · Journal of Biological Rhythms · doi:10.1177/07487304251346606 · Cited by 1
“Nevertheless, RTX did not alter the effect of TRF on the G6pc and Pck1 transcripts in the liver, most likely because the circadian regulation of those transcripts required the interaction of Per2 (not Per1 ) on Bmal1 and Rev-Erba (Le Martelot et al., 2009; Schmutz et al., 2010).”
Epigenomic and Transcriptional Regulation of Hepatic Metabolism by REV-ERB and Hdac3
Feng, D. (2013) · ScholarlyCommons (University of Pennsylvania) · Cited by 1
Mistlberger, R. E. (2015) · Wiley eBooks · doi:10.1002/9781118467831.ch4 · Cited by 1
Commentary: The Year in Circadian Rhythms
Sassone‐Corsi, P. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.95.11.9996 · Cited by 1
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Circadian Clock, Reward and Addictive Behavior
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Bode, B. (2011) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-3173
Circadian Rhythm and Food/Nutrition
Tahara, Y., & Shibata, S. (2014) · Springer eBooks · doi:10.1007/978-3-319-08945-4_13
Epigenetic Control of Circadian Clock Operation during Development
Li, C., Gong, C., Yu, S., Wu, J., & Li, X. (2012) · Genetics Research International · doi:10.1155/2012/845429
“It should be noted that different Ebox elements within their genomic context seem to differ in their affinities of CLOCK/BMAL1 binding, and direct CRY1 recruitment by CLOCK/BMAL1 to the E-box element within Dbp promoter (but not intragenic E-boxes of Dbp) has been demonstrated [100].”
The Circadian Clock and the Aging Process
Hui, K. Y., & Ripperger, J. A. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811353-0.00075-0
PER2 Mediates CREB-Dependent Light Induction of Per1Preprint
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“…the resulting PER2 protein could bind to the CO molecule via the heme group and exert a physiological effect in the form of a lack of positive effects on the expression of the BMAL1 gene, contrary to the data from cited literature (Shearman et al. 2000, Becker-Weimann et al. 2004, Yoo et al. 2004).”
ResultCircadian Rhythms and Metabolism
Grosbellet, E., & Challet, É. (2023) · Springer eBooks · doi:10.1007/978-3-319-12125-3_32-2
Circadian Rhythms and Metabolism
Grosbellet, E., & Challet, É. (2023) · Springer eBooks · doi:10.1007/978-3-031-40116-9_32
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“Each PER family member differentially regulates signaling pathways controlling cell proliferation and death and all three have been implicated in tumorigenesis at different regulatory levels (Gery et al., 2006; Schmutz et al., 2010; Grimaldi et al., 2010; Im et al., 2010).”
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BackgroundInteractions between circadian clocks and feeding behaviour
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The role of the circadian transcription factor KLF10 in liver physiology
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Metadata
- Authors
- Schmutz, I., Ripperger, J. A., Baeriswyl-Aebischer, S., & Albrecht, U.
- Affiliations
- University of Fribourg (CH)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2010-02-15
- Volume
- 24
- Issue
- 4
- Pages
- 345-357
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC2816734
- OpenAlex
- W2122503953
- Cited by
- 361
- References
- 64
- Citations by year
- 2026: 6 · 2025: 22 · 2024: 12 · 2023: 17 · 2022: 19 · 2021: 26 · 2020: 14 · 2019: 21 · 2018: 14 · 2017: 21 · 2016: 23 · 2015: 23 · 2014: 37 · 2013: 30 · 2012: 35
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- reroDoc Digital Library (submittedVersion)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Light effects on plants
- Keywords
- Per2, circadian clock, nuclear receptors, PPARα, NR1D1, co-regulation, transcriptional repression, Bmal1, HNF1A, glucose-6-phosphatase, promoter binding
- MeSH terms
- Animals, Circadian Rhythm, Gene Expression Regulation, Glucose, Liver, Promoter Regions, Genetic, Protein Binding, Receptors, Cytoplasmic and Nuclear, Mice, Knockout, Amino Acid Motifs, NIH 3T3 Cells, PPAR alpha, Mice, ARNTL Transcription Factors, Period Circadian Proteins, Nuclear Receptor Subfamily 1, Group D, Member 1
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