Cited by 2,198Circadian rhythm and melatoninLight effects on plantsPlant Molecular Biology Research

The Orphan Nuclear Receptor REV-ERBα Controls Circadian Transcription within the Positive Limb of the Mammalian Circadian Oscillator

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Preitner, Nicolas, Damiola, Francesca, Luis-Lopez-Molina, Zakany, Joszef, Duboule, Denis, Albrecht, Urs, Schibler, Ueli·2002·Cell

Abstract

Mammalian circadian rhythms are generated by a feedback loop in which BMAL1 and CLOCK, players of the positive limb, activate transcription of the cryptochrome and period genes, components of the negative limb. Bmal1 and Per transcription cycles display nearly opposite phases and are thus governed by different mechanisms. Here, we identify the orphan nuclear receptor REV-ERBalpha as the major regulator of cyclic Bmal1 transcription. Circadian Rev-erbalpha expression is controlled by components of the general feedback loop. Thus, REV-ERBalpha constitutes a molecular link through which components of the negative limb drive antiphasic expression of components of the positive limb. While REV-ERBalpha influences the period length and affects the phase-shifting properties of the clock, it is not required for circadian rhythm generation.

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Crossref · 10.1016/s0092-8674(02)00825-5

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  • CLOCK-BMAL1 dimers drive circadian transcription of Rev-erba (Nr1d1) through E-box regulatory elements; the resulting REVERBa/NR1D1 protein inhibits Bmal1 transcription through retinoic acid-related orphan receptor response elements, resulting in circadian rhythms of Bmal1 mRNA expression.

    “The best characterized of these secondary loops involves the circadian transcription of the nuclear receptor Rev-erba (Nr1d1) by CLOCK-BMAL1 dimers acting through E-box regulatory elements; the resulting REVERBa/NR1D1 protein then inhibits Bmal1 transcription through retinoic acid-related orphan receptor response elements, resulting in circadian rhythms of Bmal1 mRNA expression (21).”

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Authors
Preitner, N., Damiola, F., Luis-Lopez-Molina, Zakany, J., Duboule, D., Albrecht, U., & Schibler, U.
Affiliations
  • University of Geneva (CH)
  • University of Fribourg (CH)
Corresponding author
Schibler, Ueli
Venue
Cell
Publisher
Elsevier BV
Published
2002-07
Volume
110
Issue
2
Pages
251-260
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2104290916
Cited by
2,198
References
49
Citations by year
2026: 65 · 2025: 85 · 2024: 83 · 2023: 89 · 2022: 115 · 2021: 123 · 2020: 141 · 2019: 102 · 2018: 104 · 2017: 95 · 2016: 93 · 2015: 82 · 2014: 120 · 2013: 107 · 2012: 111
FWCI
18.72
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Archive ouverte UNIGE (University of Geneva) (publishedVersion)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Light effects on plants
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
Keywords
NR1D1, orphan nuclear receptor, circadian clock, cryptochrome, period gene, phase shifting
MeSH terms
Animals, Base Sequence, Biological Clocks, Circadian Rhythm, DNA-Binding Proteins, Eye Proteins, Flavoproteins, Gene Expression Regulation, Heart, Humans, Liver, Mice, Inbred C57BL, Molecular Sequence Data, Nuclear Proteins, Promoter Regions, Genetic, Receptors, Thyroid Hormone, RNA, Messenger, Suprachiasmatic Nucleus, Transcription Factors, Transcription, Genetic, Trans-Activators, Photoreceptor Cells, Invertebrate, DNA, Complementary, Receptors, Cytoplasmic and Nuclear, Receptors, Retinoic Acid, Mice, Knockout, Cell Cycle Proteins, Response Elements, Drosophila Proteins, Receptors, G-Protein-Coupled, Mice, Rats, Basic Helix-Loop-Helix Proteins, CLOCK Proteins, ARNTL Transcription Factors, Cryptochromes, Period Circadian Proteins, Nuclear Receptor Subfamily 1, Group F, Member 1, Nuclear Receptor Subfamily 1, Group F, Member 3

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