Molecular analysis of mammalian circadian rhythms
Abstract
In mammals, a master circadian "clock" resides in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus. The SCN clock is composed of multiple, single-cell circadian oscillators, which, when synchronized, generate coordinated circadian outputs that regulate overt rhythms. Eight clock genes have been cloned that are involved in interacting transcriptional-/translational-feedback loops that compose the molecular clockwork. The daily light-dark cycle ultimately impinges on the control of two clock genes that reset the core clock mechanism in the SCN. Clock-controlled genes are also generated by the central clock mechanism, but their protein products transduce downstream effects. Peripheral oscillators are controlled by the SCN and provide local control of overt rhythm expression. Greater understanding of the cellular and molecular mechanisms of the SCN clockwork provides opportunities for pharmacological manipulation of circadian timing.
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CLOCK and BMAL1 are transcription factors that act as positive regulators of circadian gene expression and activate expression of the negative regulators CRY and PER families.
“CLOCK and BMAL1 are transcription factors that act as positive regulators of circadian gene expression and activate the expression of the negative regulators of circadian gene expression: cryptochrome (CRY1 and CRY2) and period (PER1, PER2, PER3) families.”
From Circadian control of glucose metabolism (2014) · cites this paper as [3]
The molecular mechanism governing circadian rhythmicity is based on interlocked transcriptional and post-translational negative feedback loops.
“A number of interlocked transcriptional and post-translational negative feedback loops are responsible for the generation and maintenance of circadian rhythms.”
From Circadian control of glucose metabolism (2014) · cites this paper as [3]
CRY and PER proteins feedback and inhibit their own expression as well as the expression of other clock-controlled genes.
“CRY and PER proteins feedback and inhibit their own expression as well as the expression of other clock-controlled genes (CCGs) [3].”
From Circadian control of glucose metabolism (2014) · cites this paper as [3]
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- Authors
- Reppert, S. M., & Weaver, D. R.
- Affiliations
- Harvard University (US)
- Venue
- Annual Review of Physiology
- Publisher
- Annual Reviews
- Published
- 2001-03
- Volume
- 63
- Issue
- 1
- Pages
- 647-676
- ISSN
- 0066-4278 (ISSN-L)
- 1545-1585
- OpenAlex
- W2170078281
- Cited by
- 1,444
- References
- 152
- Citations by year
- 2026: 9 · 2025: 30 · 2024: 31 · 2023: 35 · 2022: 37 · 2021: 41 · 2020: 42 · 2019: 31 · 2018: 39 · 2017: 63 · 2016: 53 · 2015: 49 · 2014: 71 · 2013: 54 · 2012: 72
- FWCI
- 8.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Physiology (publishedVersion)
- PubMed (publishedVersion)
- 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 rhythm, suprachiasmatic nucleus, clock genes, transcription-translation feedback loop, peripheral circadian oscillators, light-dark cycle, clock-controlled genes, mammalian circadian clock
- MeSH terms
- Animals, Brain Chemistry, Circadian Rhythm, Nuclear Proteins, Suprachiasmatic Nucleus, Transcription Factors, Trans-Activators, Insect Proteins, Drosophila Proteins, Basic Helix-Loop-Helix Proteins, CLOCK Proteins, ARNTL Transcription Factors, Period Circadian Proteins
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