Molecular components of the circadian clock in mammals
Open accessAbstract
The circadian clock mechanism in animals involves a transcriptional feedback loop in which the bHLH-PAS proteins CLOCK and BMAL1 form a transcriptional activator complex to activate the transcription of the Period and Cryptochrome genes, which in turn feed back to repress their own transcription. In the mouse liver, CLOCK and BMAL1 interact with the regulatory regions of thousands of genes, which are both cyclically and constitutively expressed. The circadian transcription in the liver is clustered in phase and this is accompanied by circadian occupancy of RNA polymerase II recruitment and initiation. These changes also lead to circadian fluctuations in histone H3 lysine4 trimethylation (H3K4me3) as well as H3 lysine9 acetylation (H3K9ac) and H3 lysine27 acetylation (H3K27ac). Thus, the circadian clock regulates global transcriptional poise and chromatin state by regulation of RNA polymerase II.
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The SCN molecular clock comprises a set of transcriptional-translational feedback loops that drive rhythmic 24-h expression of the core canonical clock components.
“The SCN molecular clock comprises a set of transcriptional–translational feedback loops that drive rhythmic 24-h expression of the core canonical clock components38,39.”
From Circadian rhythm disruption and mental health (2020) · cites this paper as [39]
Members of the v-Cry/Cry2/tr-Cry family function as transcriptional repressors in the circadian transcription/translational core loop.
“whereas members of the distinct v-Cry/Cry2/tr-Cry family function as transcriptional repressors in the circadian transcription/translational core loop [reviewed in Ref. (37)].”
From An Overview of Monthly Rhythms and Clocks (2017) · cites this paper as [37]
In all nucleated cells, four families of core clock genes (Clock, Bmal1, Period, and Cryptochrome) form a transcription-translation feedback loop that cycles every approximately 24 hours.
“In all nucleated cells, four families of core clock genes (Clock, Bmal1, Period [Per], and Cryptochrome [Cry]) form a transcriptiontranslation feedback loop that cycles every approximately 24 hours (reviewed in refs.[28][29][30][31][32][33][34][35].”
From Role of the circadian system in cardiovascular disease (2018) · cites this paper as [28]
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- Authors
- Takahashi, J. S.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Takahashi, J. S.
- ORCID
- Takahashi, J. S.
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2015-09
- Volume
- 17
- Issue
- S1
- Pages
- 6-11
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- PMC
- PMC4560116
- OpenAlex
- W1930786993
- Cited by
- 230
- References
- 41
- Citations by year
- 2026: 14 · 2025: 17 · 2024: 15 · 2023: 17 · 2022: 22 · 2021: 24 · 2020: 24 · 2019: 28 · 2018: 28 · 2017: 27 · 2016: 12 · 2014: 1
- FWCI
- 2.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Diabetes Obesity and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute on Aging (R01AG045795)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Keywords
- circadian clock, transcriptional feedback loop, clocks, Bmal1, bHLH-PAS proteins, period gene, mouse liver, circadian gene expression, RNA polymerase II recruitment, histone modifications, H3K4me3, H3K9ac, H3K27ac, chromatin state
- MeSH terms
- Acetylation, Animals, Histones, Humans, Liver, Lysine, Mammals, Models, Biological, RNA Polymerase II, Transcription, Genetic, Gene Expression, Mice, Basic Helix-Loop-Helix Proteins, CLOCK Proteins, ARNTL Transcription Factors, Circadian Clocks
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