GO:0007623 circadian rhythm: Biological Process, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0007623 circadian rhythm is defined as any biological process in an organism that recurs with a regularity of approximately 24 hours.
• Circadian rhythms are generated by a cell-autonomous molecular clock built on interlocking transcriptional-translational feedback loops of clock genes such as CLOCK, BMAL1 (ARNTL), PER1-3, CRY1-2, NR1D1 and RORA.
• Disruption of circadian rhythm is linked to sleep-wake disorders, hypertension, cancer and other human pathologies.
• Melatonin is a key hormonal output of the circadian system and is widely used to study and restore rhythm.
• Host genetics shape circadian phenotype, making clock genes tractable targets for functional genomics.
• CRISPR knockout, point-mutation, knock-in and overexpression models enable causal testing of clock gene function in cells and animals.
Description
Circadian rhythm (GO:0007623) is a fundamental biological process that recurs with a period of approximately 24 hours, allowing organisms to anticipate and adapt to daily environmental cycles. This process governs sleep-wake behavior, hormone secretion, body temperature, blood pressure and many metabolic functions, and its disruption is increasingly recognized as a contributor to human disease. For researchers, circadian rhythm represents a genetically tractable system in which defined clock genes drive measurable, rhythmic outputs that can be perturbed and quantified. Understanding the molecular architecture of the circadian clock is therefore essential for chronobiology, sleep medicine, cardiovascular research and oncology.
circadian rhythm At A Glance
| GO ID | GO:0007623 |
|---|---|
| GO term | circadian rhythm |
| Ontology | biological_process |
| Synonym | circadian process; circadian response; response to circadian rhythm |
| Definition | Any biological process in an organism that recurs with a regularity of approximately 24 hours |
| Major function | Generation and regulation of endogenous ~24-hour biological oscillations |
| Representative genes | CLOCK, ARNTL (BMAL1), PER1, PER2, PER3, CRY1, CRY2, NR1D1, RORA |
| Associated disorders | Circadian rhythm sleep-wake disorders, hypertension, cancer |
| Research methods | CRISPR knockout/knock-in, RNA-seq, bioluminescence reporter imaging, melatonin assays |
What Is GO:0007623?
In the Gene Ontology, circadian rhythm (GO:0007623) is defined as any biological process in an organism that recurs with a regularity of approximately 24 hours. It encompasses the endogenous timekeeping mechanism, the entrainment of that mechanism by environmental cues, and the rhythmic physiological and behavioral outputs it controls.
Why Is circadian rhythm Important in Cell Biology?
Circadian rhythm is important because it coordinates physiology with the daily environment, and its dysregulation is associated with sleep-wake disorders, cardiovascular disease and cancer. Because the core clock is genetically encoded, it provides a defined set of gene targets for mechanistic studies and therapeutic development.
• Circadian rhythm sleep-wake disorders are a major clinical category requiring accurate diagnosis and treatment.
• Melatonin is a central hormonal mediator of circadian timing and a target for rhythm restoration.
• Circadian disruption in older adults contributes to sleep-wake disorders in that population.
• Clock genes regulate blood pressure and are implicated in hypertension.
• Circadian rhythm is linked to cancer biology and tumor progression.
• Intraocular pressure shows a circadian rhythm relevant to glaucoma research.
• Host genetics influence circadian phenotype and disease susceptibility.
• Clock genes provide tractable targets for CRISPR-based functional studies.
What Happens During circadian rhythm?
Entrainment to environmental cues
In simple terms: The clock is reset each day by external signals such as light.
Circadian rhythms are synchronized to the environment primarily by light, which entrains the central clock and aligns internal timing with the external day. Melatonin secretion is a key rhythmic output that reflects and reinforces this entrainment.
Core transcriptional-translational feedback loop
In simple terms: Clock proteins turn each other on and off in a daily cycle.
The core clock is built on interlocking feedback loops in which CLOCK and BMAL1 activate PER and CRY genes, whose protein products feedback to inhibit their own transcription, generating ~24-hour oscillations.
Rhythmic physiological outputs
In simple terms: The clock drives daily changes in body functions.
The clock regulates diverse outputs including sleep-wake behavior, blood pressure and intraocular pressure, linking molecular timing to organ-level physiology.
Aging and disease-associated remodeling
In simple terms: The clock changes with age and disease.
Circadian rhythm sleep-wake disorders are common in older adults, and circadian dysregulation is associated with hypertension and cancer, indicating that clock function is remodeled in aging and disease.
Key Genes Involved in GO:0007623 circadian rhythm
The following genes encode core clock components and regulators that are central to circadian rhythm research.
| Gene | Major Role | Research Relevance |
|---|---|---|
| CLOCK | Core transcriptional activator of the clock | Central to clock mechanism studies |
| ARNTL (BMAL1) | Core transcriptional activator partnering with CLOCK | Essential clock gene for knockout studies |
| PER1 | Negative regulator in the core feedback loop | Rhythm amplitude and period research |
| PER2 | Negative regulator in the core feedback loop | Circadian period and disease studies |
| PER3 | Clock component implicated in sleep regulation | Sleep-wake disorder research |
| CRY1 | Negative regulator of CLOCK/BMAL1 | Clock repression studies |
| CRY2 | Negative regulator of CLOCK/BMAL1 | Clock repression studies |
| NR1D1 (REV-ERBα) | Accessory loop regulator of clock output | Metabolic and clock regulation research |
| RORA | Accessory loop transcriptional regulator | Clock gene regulation studies |
| MTNR1A | Melatonin receptor mediating rhythmic signaling | Melatonin and rhythm restoration research |
| MTNR1B | Melatonin receptor mediating rhythmic signaling | Melatonin and rhythm restoration research |
| AANAT | Enzyme in melatonin synthesis | Melatonin production studies |
| ASMT | Enzyme in melatonin synthesis | Melatonin production studies |
| TPH1 | Serotonin pathway enzyme upstream of melatonin | Melatonin synthesis research |
| OPN4 | Photoreceptor for light entrainment | Light entrainment studies |
| GENE_HOST | Host genetic factors influencing circadian phenotype | Host genetics and circadian research |
How Is circadian rhythm Regulated?
Circadian rhythm is regulated by interlocking transcriptional-translational feedback loops of core clock genes, and is entrained by environmental light. Melatonin provides an endocrine regulatory signal that can restore or modulate rhythmicity. Host genetic variation further shapes circadian regulation.
circadian rhythm and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| CLOCK | Circadian rhythm sleep-wake disorders | Knockout cell and animal models |
| ARNTL (BMAL1) | Hypertension and clock disruption | Knockout and knock-in models |
| PER2 | Cancer and circadian dysregulation | Point-mutation and knockout models |
| MTNR1B | Melatonin signaling and rhythm disorders | Overexpression and knockout models |
| CRY1 | Sleep-wake and metabolic phenotypes | Knock-in and knockout models |
Circadian rhythm sleep-wake disorders
Circadian rhythm sleep-wake disorders arise from misalignment between the endogenous clock and the external environment, and are a major clinical focus of circadian research. These disorders are particularly prevalent in older adults.
Hypertension and cardiovascular disease
Clock genes regulate blood pressure, and circadian rhythm disruption is implicated in hypertension, linking molecular timing to cardiovascular pathology.
Cancer
Circadian rhythm dysregulation is associated with cancer biology, and clock genes are studied as modulators of tumor progression.
Ocular disease
Intraocular pressure exhibits a circadian rhythm, making circadian biology relevant to glaucoma and ocular physiology research.
From circadian rhythm-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Is a clock gene required for rhythmicity? | CRISPR knockout cell line |
| Does a specific variant alter clock period? | CRISPR point-mutation knock-in |
| Where and when is a clock protein expressed? | Tagged knock-in reporter |
| Does overexpression shift rhythm amplitude? | CRISPR overexpression model |
| Which genes are rhythmic genome-wide? | CRISPR library screening with RNA-seq readout |
| How does host genetics shape rhythm? | Knockout panel and bioinformatic analysis |
How to Study the circadian rhythm Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Bioluminescence reporter imaging | Rhythmic clock gene expression | Clock oscillation studies |
| RNA-seq | Rhythmic transcriptome | Clock target discovery |
| Melatonin assay | Endocrine rhythm output | Rhythm restoration research |
| CRISPR knockout | Gene requirement for rhythm | Causal clock gene testing |
| CRISPR knock-in | Variant effect on rhythm | Period and amplitude studies |
| CRISPR overexpression | Gain-of-function rhythm effects | Amplitude modulation studies |
| CRISPR library screening | Genome-wide rhythm regulators | Functional genomics |
| Bioinformatics | Rhythmicity and pathway enrichment | Clock network analysis |
Bioluminescence reporter imaging
Reporter imaging of clock gene promoters allows real-time monitoring of circadian oscillations in cultured cells and tissues.
RNA sequencing
RNA-seq identifies rhythmic transcripts and reveals how clock gene perturbation reshapes the transcriptome.
Melatonin measurement
Melatonin assays assess the endocrine output of the circadian system and are used in rhythm restoration studies.
CRISPR functional genomics
CRISPR knockout, knock-in and overexpression combined with sequencing enable causal testing of clock gene function.
How CRISPR Can Be Used to Study GO:0007623 circadian rhythm
Knockout
CRISPR knockout of core clock genes such as CLOCK or ARNTL abolishes or alters rhythmicity, providing direct causal evidence for their role in circadian rhythm.
Point Mutation
CRISPR point mutation can model disease-associated or functional variants in clock genes to test their effect on period and amplitude.
Knock-in
Knock-in of reporters or tagged alleles enables visualization and biochemical analysis of clock proteins in their endogenous context.
Overexpression
CRISPR-mediated overexpression of clock regulators tests gain-of-function effects on rhythm amplitude and output.
How EDITGENE Supports circadian rhythm Research
Researchers studying circadian rhythm-related genes often need to determine whether a candidate gene is causally involved in generating or modulating ~24-hour oscillations, and CRISPR-based models provide the most direct route to that answer.
Contact EDITGENE today to design your custom CRISPR model for circadian rhythm research.
Frequently Asked Questions About circadian rhythm
What is circadian rhythm GO:0007623?
GO:0007623 circadian rhythm is defined as any biological process in an organism that recurs with a regularity of approximately 24 hours.
What genes are involved in circadian rhythm?
Core clock genes include CLOCK, ARNTL (BMAL1), PER1-3, CRY1-2, NR1D1 and RORA.
How is circadian rhythm regulated?
It is regulated by interlocking transcriptional-translational feedback loops and entrained by light, with melatonin as a key endocrine signal.
What diseases are linked to circadian rhythm disruption?
Circadian rhythm sleep-wake disorders, hypertension and cancer are associated with circadian disruption.
How do you study circadian rhythm in the lab?
Common approaches include bioluminescence reporter imaging, RNA-seq, melatonin assays and CRISPR functional genomics.
What is the role of melatonin in circadian rhythm?
Melatonin is a hormonal output of the circadian system and is used to study and restore rhythm.
Does circadian rhythm change with age?
Circadian rhythm sleep-wake disorders are common in older adults, indicating age-related changes in circadian function.
Can CRISPR be used to study circadian rhythm genes?
Yes, CRISPR knockout, knock-in, point-mutation and overexpression models enable causal testing of clock gene function.
What is the relationship between circadian rhythm and cancer?
Circadian rhythm dysregulation is associated with cancer biology and tumor progression.
Why is host genetics important for circadian rhythm?
Host genetic variation shapes circadian phenotype and disease susceptibility.
Conclusion
Circadian rhythm (GO:0007623) is a genetically encoded ~24-hour biological process that coordinates physiology with the environment and is implicated in sleep-wake disorders, hypertension and cancer. CRISPR-based models provide a powerful framework for dissecting the causal roles of clock genes and for developing rhythm-targeted interventions.
References
- 1. Sun SY et al.. 2022. Treatment of Circadian Rhythm Sleep-Wake Disorders.. Curr Neuropharmacol 20(6):1022-1034 PMID: 34493186
- 2. Vasey C et al.. 2021. Circadian Rhythm Dysregulation and Restoration: The Role of Melatonin.. Nutrients 13(10) PMID: 34684482
- 3. Kim JH et al.. 2022. Circadian Rhythm Sleep-Wake Disorders in Older Adults.. Sleep Med Clin 17(2):241-252 PMID: 35659077
- 4. Costello HM et al.. 2021. Circadian Rhythm, Clock Genes, and Hypertension: Recent Advances in Hypertension.. Hypertension 78(5):1185-1196 PMID: 34601963
- 5. Munteanu C et al.. 2024. The Relationship between Circadian Rhythm and Cancer Disease.. Int J Mol Sci 25(11) PMID: 38892035
- 6. Ikegami K. 2024. Circadian rhythm of intraocular pressure.. J Physiol Sci 74(1):14 PMID: 38431563
- 7. Zee PC et al.. 2020. Circadian Rhythm Sleep-Wake Disorders.. Continuum (Minneap Minn) 26(4):988-1002 PMID: 32756232
- 8. Odriozola A et al.. 2024. Circadian rhythm and host genetics.. Adv Genet 111:451-495 PMID: 38908904
