ArticleToxicological sciences : an official journal of the Society of Toxicology2010
Disruption of CLOCK-BMAL1 transcriptional activity is responsible for aryl hydrocarbon receptor-mediated regulation of Period1 gene.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 67 citations in OpenAlex.
- Circadian synchronization between diet and gut microbiota in modulating host's health.Gut microbes · 2026Review
- The CLOCK-BMAL1 complex in circadian regulation: structure, mechanisms, and therapeutic targeting.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Functional genomic analysis of non-canonical DNA regulatory elements of the aryl hydrocarbon receptor.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Reimagining AHR in Cancer: From Environmental Sensor to Novel Immunomodulatory Therapeutic Target.International journal of biological sciences · 2026Review
- Functional genomic analysis of non-canonical DNA regulatory elements of the aryl hydrocarbon receptor.bioRxiv : the preprint server for biology · 2025Article
- Review
- Aryl Hydrocarbon Receptor Involvement in the Sodium-Dependent Glutamate/Aspartate Transporter Regulation in Cerebellar Bergmann Glia Cells.ACS chemical neuroscience · 2024Article
- Activation of aryl hydrocarbon receptor (AhR) in Alzheimer's disease: role of tryptophan metabolites generated by gut host-microbiota.Journal of molecular medicine (Berlin, Germany) · 2023Review
- Aryl Hydrocarbon Receptor in Glia Cells: A Plausible Glutamatergic Neurotransmission Orchestrator.Neurotoxicity research · 2023Review
- Aryl hydrocarbon receptor affects circadian-regulated lipolysis through an E-Box-dependent mechanism.Molecular and cellular endocrinology · 2023Article
- Insight into the physiological and pathological roles of the aryl hydrocarbon receptor pathway in glucose homeostasis, insulin resistance, and diabetes development.Cellular & molecular biology letters · 2022Review
- Structures of NPAS4-ARNT and NPAS4-ARNT2 heterodimers reveal new dimerization modalities in the bHLH-PAS transcription factor family.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- TCDD exposure alters fecal IgA concentrations in male and female mice.BMC pharmacology & toxicology · 2022Article
- Circadian rhythms and renal pathophysiology.The Journal of clinical investigation · 2022Review
- Aryl hydrocarbon receptor: Its roles in physiology.Biochemical pharmacology · 2021Review
- Pharmacological Actions of Carbamate Insecticides at Mammalian Melatonin Receptors.The Journal of pharmacology and experimental therapeutics · 2021Article
- Cross-species physiological interactions of endocrine disrupting chemicals with the circadian clock.General and comparative endocrinology · 2021Review
- The Landscape of AhR Regulators and Coregulators to Fine-Tune AhR Functions.International journal of molecular sciences · 2021Review
- Circadian Host-Microbiome Interactions in Immunity.Frontiers in immunology · 2020Review
- Mechanisms of circadian clock interactions with aryl hydrocarbon receptor signalling.The European journal of neuroscience · 2020Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The aryl hydrocarbon receptor (AhR) is a period-aryl hydrocarbon receptor nuclear transporter-simple minded domain transcription factor that shares structural similarity with circadian clock genes and readily interacts with components of the molecular clock. Activation of AhR by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters behavioral circadian rhythms and represses the Period1 (Per1) gene in murine hematopoietic stem and progenitor cells. Per1 expression is driven by circadian locomotor activity cycles kaput-brain muscle ARNT-like (CLOCK-BMAL1)-dependent activation of Eboxes in the Per1 promoter. We hypothesized that the effects of AhR activation on the circadian clock are mediated by disruption of CLOCK-BMAL1 function and subsequent Per1 gene suppression. Effects of AhR activation on rhythmic Per1 transcripts were examined in livers of mice after treatment with the AhR agonist, TCDD; the molecular mechanisms of Per1 repression by AhR were determined in hepatoma cells using TCDD and beta-napthoflavone as AhR activators. This study reports, for the first time, that AhR activation by TCDD alters the Per1 rhythm in the mouse liver and that Per1 gene suppression depends upon the presence of AhR. Furthermore, AhR interaction with BMAL1 attenuates CLOCK-BMAL1 activity and decreases CLOCK binding at Ebox1 and Ebox3 in the Per1 promoter. Taken together, these data suggest that AhR activation represses Per1 through disrupting CLOCK-BMAL1 activity, producing dysregulation of rhythmic Per1 gene expression. These data define alteration of the Per1 rhythm as novel signaling events downstream of AhR activation. Downregulation of Per1 could contribute to metabolic disease, cancer, and other detrimental effects resulting from exposure to certain environmental pollutants.
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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.