A circadian gene expression atlas in mammals: Implications for biology and medicine
Open accessAbstract
Significance: We generated high-resolution multiorgan expression data showing that nearly half of all genes in the mouse genome oscillate with circadian rhythm somewhere in the body. Such widespread transcriptional oscillations have not been previously reported in mammals. Applying pathway analysis, we observed new clock-mediated spatiotemporal relationships. Moreover, we found a majority of best-selling drugs in the United States target circadian gene products. Many of these drugs have relatively short half-lives, and our data predict which may benefit from timed dosing.
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Isolations were performed at the same time of day to limit circadian variation.
“Isolations were performed at the same time of day to limit circadian variation, which affects the expression of nearly half of all murine genes (Zhang et al. 2014).”
From Murine single-cell RNA-seq reveals cell-identity- and tissue-specific trajectories of aging (2019) · cites this paper as Zhang et al. 2014
The Zhang et al. dataset contains 8 replicates of 12 tissues types collected for a single study under controlled conditions.
“This dataset contains 8 replicates of 12 tissues types collected for a single study under controlled conditions.”
From Osteocyte transcriptome mapping identifies a molecular landscape controlling skeletal homeostasis and susceptibility to skeletal disease (2021) · cites this paper as [28]
Mouse gastrocnemius muscles show four- to ten-fold differences in mRNA expression from peak to trough over the time of day.
“Data from mouse gastrocnemius muscles collected every 2 h for 48 h demonstrate four to ten-fold differences in gene expression from peak to trough in messenger RNA expression over the time of day (Zhang et al., 2014).”
From Myosteatosis in the Context of Skeletal Muscle Function Deficit: An Interdisciplinary Workshop at the National Institute on Aging (2020) · cites this paper as Zhang et al., 2014
Many of the most effective treatments for brain disorders and other diseases modulate clock function.
“Many of the most effective treatments for brain disorders and other diseases modulate clock function216,326,330,332,333.”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [332]
Approximately 13% of protein-coding genes in the kidney are rhythmic.
“The kidney is essential to long-term regulation of BP and approximately 13% of protein-coding genes in the kidney are rhythmic (41).”
From Role of the circadian system in cardiovascular disease (2018) · cites this paper as [41]
In any given mammalian tissue, approximately 5%-15% of gene transcripts are rhythmic, with some differences in the specific cycling genes between tissues, with 43% of protein-coding genes being rhythmic in at least one tissue.
“In any given mammalian tissue, approximately 5%-15% of gene transcripts are rhythmic, with some differences in the specific cycling genes between tissues, with 43% of protein-coding genes being rhythmic in at least one tissue (41).”
From Role of the circadian system in cardiovascular disease (2018) · cites this paper as [41]
Gene expression is rhythmic for the targets of the majority of top-selling and essential medications listed by the World Health Organization, including angiotensin II receptor blockers, β-adrenoreceptor antagonists, and aldosterone receptor blockers.
“Indeed, gene expression is rhythmic for the targets of the majority of top-selling and essential medications listed by the World Health Organization (41), including angiotensin II receptor blockers, β-adrenoreceptor antagonists, and aldosterone receptor blockers (41).”
From Role of the circadian system in cardiovascular disease (2018) · cites this paper as [41]
Mouse expression of cyclooxygenase-1 (COX-1), a target for aspirin, exhibits circadian rhythms in several tissues including the heart.
“Of note, mouse expression of cyclooxygenase-1 (COX-1), a target for aspirin, exhibits circadian rhythms in several tissues including the heart (41).”
From Role of the circadian system in cardiovascular disease (2018) · cites this paper as [41]
Analysis of the mouse transcriptome in 12 organs revealed that 43% of all protein coding genes exhibit circadian rhythmicity in one or more tissues.
“Many of these genes are rhythmic in a tissue-specific context, and recent analysis of mouse transcriptome in 12 organs revealed that 43% of all protein coding genes exhibit circadian rhythmicity in one or more tissues (30).”
From Circadian rhythms, metabolism, and chrononutrition in rodents and humans (2016) · cites this paper as [30]
The finding on transcriptional variability is in line with Warren et al. but in contrast to other studies that suggested increased transcriptional variability is a common feature of aging.
“This is in line with Warren et al. 51 , but in contrast to other studies that suggested increased transcriptional variability is a common feature of aging 34,52 .”
From Single-cell transcriptomic profiling of the aging mouse brain (2019) · cites this paper as [51]
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“oreover, many of the most widely used drugs target the products f these rhythmic genes (Zhang et al., 2014).”
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- Authors
- Zhang, R., Lahens, N. F., Ballance, H. I., Hughes, M. E., & Hogenesch, J. B.
- Affiliations
- University of Pennsylvania (US)
- University of Missouri–St. Louis (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-10-27
- Volume
- 111
- Issue
- 45
- Pages
- 16219-16224
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4234565
- OpenAlex
- W2133918896
- Cited by
- 2,304
- References
- 51
- Citations by year
- 2026: 168 · 2025: 209 · 2024: 225 · 2023: 211 · 2022: 224 · 2021: 258 · 2020: 266 · 2019: 201 · 2018: 171 · 2017: 155 · 2016: 120 · 2015: 85 · 2014: 9 · 2012: 1
- FWCI
- 60.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pennsylvania Department of Health
- University of Pennsylvania
- Institute for Translational Medicine and Therapeutics
- National Institutes of Health
- Defense Advanced Research Projects Agency
- National Heart, Lung, and Blood Institute (HL 097800, R01HL097800, T32 5T32HL007953-13, T32HL007953)
- National Human Genome Research Institute (T32HG000046)
- National Institute of Neurological Disorders and Stroke (R01NS054794)
- National Institute of Environmental Health Sciences (P30ES013508)
- 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 clock, circadian gene expression, clock genes, drug timing, chronotherapy, elimination half-life, mouse transcriptome
- MeSH terms
- Animals, Circadian Rhythm, Gene Expression Regulation, Humans, Chronotherapy, Gene Expression Profiling, Databases, Nucleic Acid, Mice, Transcriptome
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