ArticleProceedings of the National Academy of Sciences of the United States of America2018
Nuclear receptor HNF4A transrepresses CLOCK:BMAL1 and modulates tissue-specific circadian networks.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 87 citations in OpenAlex.
- Circadian rhythms in major depressive disorder: mechanistic insights and therapeutic frontiers.Annals of medicine · 2026Review
- BMAL1 silencing as a promising chemosensitizing strategy for triple-negative breast cancer.Acta pharmacologica Sinica · 2026Article
- Timing the strain: skeletal muscle clock as regulator of physical activity.npj metabolic health and disease · 2026Review
- OCT4-driven PER1 activation promotes odontogenic differentiation in senescent SCAP spheres.International journal of oral science · 2026Article
- Circadian biology and exercise: the time to move.Life metabolism · 2026Review
- Diurnal Regulation and Gene-Specific Vulnerability of Oxidative Alcohol-Metabolizing Enzymes to Circadian Disruption.International journal of molecular sciences · 2026Article
- Glucocorticoid-dependence and independence of the circadian liver transcriptome.Npj biological timing and sleep · 2026Article
- Review
- Temporal Dynamics of the Plasma Proteomic Landscape Reveals Maladaptation in ME/CFS Following Exertion.Molecular & cellular proteomics : MCP · 2025Article
- Targeting the hepatic circadian clock concomitant with tyrosine kinase inhibition reverses late-stage hepatocellular carcinoma.Cell reports · 2025Article
- Crosstalk between the circadian clock, intestinal stem cell niche, and epithelial cell fate decision.Genes & diseases · 2025Review
- The interplay between circadian rhythms and aging: molecular mechanisms and therapeutic strategies.Biogerontology · 2025Review
- Hepatocyte Nuclear Factor 4 Alpha: A Key Regulator of Liver Disease Pathology and Haemostatic Disorders.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Abundant repressor binding sites in human enhancers are associated with the fine-tuning of gene regulation.iScience · 2025Article
- Liver as a nexus of daily metabolic cross talk.International review of cell and molecular biology · 2025Review
- Liver-gut axis signaling regulates circadian energy metabolism in shift workers.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Cell-specific regulation of the circadian clock by BMAL1 in the paraventricular nucleus: Implications for regulation of systemic biological rhythms.Cell reports · 2024Article
- Circadian-driven tissue specificity is constrained under caloric restricted feeding conditions.Communications biology · 2024Article
- Downregulation of HNF4A enables transcriptomic reprogramming during the hepatic acute-phase response.Communications biology · 2024Article
- The emergence of circadian timekeeping in the intestine.Nature communications · 2024Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Either expression level or transcriptional activity of various nuclear receptors (NRs) have been demonstrated to be under circadian control. With a few exceptions, little is known about the roles of NRs as direct regulators of the circadian circuitry. Here we show that the nuclear receptor HNF4A strongly transrepresses the transcriptional activity of the CLOCK:BMAL1 heterodimer. We define a central role for HNF4A in maintaining cell-autonomous circadian oscillations in a tissue-specific manner in liver and colon cells. Not only transcript level but also genome-wide chromosome binding of HNF4A is rhythmically regulated in the mouse liver. ChIP-seq analyses revealed cooccupancy of HNF4A and CLOCK:BMAL1 at a wide array of metabolic genes involved in lipid, glucose, and amino acid homeostasis. Taken together, we establish that HNF4A defines a feedback loop in tissue-specific mammalian oscillators and demonstrate its recruitment in the circadian regulation of metabolic pathways.
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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.