ArticlePLoS genetics2021
NF-κB modifies the mammalian circadian clock through interaction with the core clock protein BMAL1.
Article in PLoS genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 82 citations in OpenAlex.
- Circadian synchronization between diet and gut microbiota in modulating host's health.Gut microbes · 2026Review
- Biological Rhythms in Coronavirus Pneumonia Pathogenesis.Journal of biological rhythms · 2026Article
- Neuroinflammatory suppression of astrocytic BMAL1 defines a selective reactive astrocyte program.Journal of neuroinflammation · 2026Article
- Temporal Vulnerability of the Blood-Brain Interface in Stroke: Molecular Mechanisms of Circadian Dynamics, Inflammation, and Aging.International journal of molecular sciences · 2026Review
- Multi-omic analysis reveals Wharton's jelly mesenchymal stem cells shift the pro-inflammatory phenotype of fibroblast subpopulation to induce skin rejuvenation.Cell & bioscience · 2026Article
- Time vortex: the circadian-dopaminergic dialogue in Parkinson's disease.NPJ Parkinson's disease · 2026Review
- Multi-Omics Landscape of Circadian Clock Dysregulation Across the Chronic Liver Disease Spectrum.International journal of molecular sciences · 2026Review
- Therapeutic Strategies Targeting the Kidney-Liver-Immune-Heart Network: Circadian and Mechanosensory Pathways in CKD-Associated Cardiac Injury.International journal of molecular sciences · 2026Review
- The clockwork macrophage: Timing in innate immunity.Biomedical journal · 2026Review
- A temporal dialogue between the circadian clock and chronic inflammatory diseases.Disease models & mechanisms · 2026Review
- Lack of GPNMB Is Associated With Altered Lipid and Glucose Metabolism and Disrupted Diurnal Hepatic Glycogen Regulation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Protein Acylation Modifications in Sleep Disorders: Mechanisms and Therapeutic Potential.Journal of molecular neuroscience : MN · 2026Review
- Gut microbiota circadian rhythms: a key regulator of immunometabolic homeostasis.Acta biochimica et biophysica Sinica · 2026Review
- The pivotal role and intervention strategies of BMAL1 mediated circadian clock dysregulation in intervertebral disc degeneration.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- The Circadian Transcription Factor CLOCK Modulates Oxidative Stress Resistance via the ACHL-Relish Axis in Drosophila.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The oral immune and inflammatory network under circadian clock control.Frontiers in immunology · 2026Review
- Circadian clock-gut microbiota axis in pulmonary hypertension: linking gut-lung crosstalk, immune timing and vascular remodeling.Frontiers in physiology · 2026Review
- Autonomous Oscillations of NF-κB.Advances in experimental medicine and biology · 2026Review
- Astrocyte-blood-brain barrier crosstalk in cerebral small vessel disease: linking barrier dysfunction to neurovascular failure.Frontiers in neurology · 2026Review
- Core Circadian Protein BMAL1: Implication for Nervous System Functioning and Its Diseases.Brain sciences · 2025Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
In mammals, the circadian clock coordinates cell physiological processes including inflammation. Recent studies suggested a crosstalk between these two pathways. However, the mechanism of how inflammation affects the clock is not well understood. Here, we investigated the role of the proinflammatory transcription factor NF-κB in regulating clock function. Using a combination of genetic and pharmacological approaches, we show that perturbation of the canonical NF-κB subunit RELA in the human U2OS cellular model altered core clock gene expression. While RELA activation shortened period length and dampened amplitude, its inhibition lengthened period length and caused amplitude phenotypes. NF-κB perturbation also altered circadian rhythms in the master suprachiasmatic nucleus (SCN) clock and locomotor activity behavior under different light/dark conditions. We show that RELA, like the clock repressor CRY1, repressed the transcriptional activity of BMAL1/CLOCK at the circadian E-box cis-element. Biochemical and biophysical analysis showed that RELA binds to the transactivation domain of BMAL1. These data support a model in which NF-kB competes with CRY1 and coactivator CBP/p300 for BMAL1 binding to affect circadian transcription. This is further supported by chromatin immunoprecipitation analysis showing that binding of RELA, BMAL1 and CLOCK converges on the E-boxes of clock genes. Taken together, these data support a significant role for NF-κB in directly regulating the circadian clock and highlight mutual regulation between the circadian and inflammatory pathways.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.