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MAMMALIAN CIRCADIAN BIOLOGY: Elucidating Genome-Wide Levels of Temporal Organization
Open accessAbstract
During the past decade, the molecular mechanisms underlying the mammalian circadian clock have been defined. A core set of circadian clock genes common to most cells throughout the body code for proteins that feed back to regulate not only their own expression, but also that of clock output genes and pathways throughout the genome. The circadian system represents a complex multioscillatory temporal network in which an ensemble of coupled neurons comprising the principal circadian pacemaker in the suprachiasmatic nucleus of the hypothalamus is entrained to the daily light/dark cycle and subsequently transmits synchronizing signals to local circadian oscillators in peripheral tissues. Only recently has the importance of this system to the regulation of such fundamental biological processes as the cell cycle and metabolism become apparent. A convergence of data from microarray studies, quantitative trait locus analysis, and mutagenesis screens demonstrates the pervasiveness of circadian regulation in biological systems. The importance of maintaining the internal temporal homeostasis conferred by the circadian system is revealed by animal models in which mutations in genes coding for core components of the clock result in disease, including cancer and disturbances to the sleep/wake cycle.
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“At the molecular level, the central clock (in the suprachiasmatic nucleus) and peripheral oscillators throughout the body comprise a self-sustaining network of transcriptional-translational feedback loops that drive 24-hour expression patterns of core clock genes (47).”
From Social jetlag, chronotype, and cardiometabolic risk (2015) · cites this paper as [47]
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Metadata
- Authors
- Lowrey, P. L., & Takahashi, J. S.
- Affiliations
- Northwestern University (US)
- ORCID
- Takahashi, Joseph S.
- Venue
- Annual Review of Genomics and Human Genetics
- Publisher
- Annual Reviews
- Published
- 2004-09-22
- Volume
- 5
- Issue
- 1
- Pages
- 407-441
- ISSN
- 1527-8204 (ISSN-L)
- 1545-293X
- PMC
- PMC3770722
- OpenAlex
- W2123789196
- Cited by
- 976
- References
- 242
- Citations by year
- 2026: 8 · 2025: 30 · 2024: 28 · 2023: 29 · 2022: 29 · 2021: 29 · 2020: 48 · 2019: 27 · 2018: 40 · 2017: 42 · 2016: 35 · 2015: 38 · 2014: 65 · 2013: 53 · 2012: 62
- FWCI
- 5.61
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Annual Review of Genomics and Human Genetics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- mammalian circadian clock, clock genes, suprachiasmatic nucleus, peripheral circadian oscillators, light-dark cycle entrainment, cell cycle regulation, metabolism, cancer, sleep-wake cycle, quantitative trait loci, mutagenesis screen
- MeSH terms
- Animals, Circadian Rhythm, Humans, Mammals, Sleep, Wakefulness, Genome
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