ArticleGenes & development2012
Rev-erbα and Rev-erbβ coordinately protect the circadian clock and normal metabolic function.
Article in Genes & development, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 313 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
313 citing papers in PubMed, 2 syntheses or guidelines pooled it, 500 citations in OpenAlex.
- Genetic variation of clock genes and cancer risk: a field synopsis and meta-analysis.Oncotarget · 2017Pooled it
- Machine learning identifies a compact gene set for monitoring the circadian clock in human blood.Genome medicine · 2017Pooled it
- Circadian synchronization between diet and gut microbiota in modulating host's health.Gut microbes · 2026Review
- Loss of hepatic circadian organization in fatty liver syndrome identifies CLOCK as a regulator of lipid homeostasis in laying hens.Poultry science · 2026Article
- Disruption of SWI/SNF ATPases in the mouse liver impairs diurnal gene expression associated with specific promoter features.Nature communications · 2026Article
- The circadian clock controls hepatic stellate cell activation via a BMAL1/CK1ε/REV-ERBα/transgelin signaling pathway.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The circadian architecture of tumor immunity: mechanistic insights and treatment strategies.Biomarker research · 2026Review
- NR5A2 controls gene expression and chromatin contacts of essential circadian metabolic genes in the liver.Cellular and molecular life sciences : CMLS · 2026Article
- Article
- Circadian disruption as a driver and target in neurodegenerative diseases: from molecular mechanisms to chronotherapeutic strategies.Metabolic brain disease · 2026Review
- REV-ERB-alpha and -beta coordinately regulate astrocyte reactivity and proteostatic function.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Negative regulation of TbioRxiv : the preprint server for biology · 2026Article
- Targeting nuclear receptors in muscular dystrophies and regenerative myogenesis.Frontiers in cell and developmental biology · 2026Review
- Short-term continuous light exposure induces hippocampal rhythmic and functional alterations: a multi-timepoint metabolomics study.Frontiers in molecular biosciences · 2026Article
- REV-ERBs as regulators of circadian rhythm, neuroinflammation, and glial lipid homeostasis in Alzheimer's disease. A narrative review.British journal of biomedical science · 2026Review
- The importance of sex dimorphism in liver metabolism and progressive liver diseases.Biology of sex differences · 2025Review
- REV-ERBα regulates brain NADNature aging · 2025Article
- Perturbation of the circadian clock in chronic diseases involving organ fibrosis.The Journal of clinical investigation · 2025Review
- Circadian circuits control plasticity of group 3 innate lymphoid cells by sustaining epigenetic configuration of RORγt.Nature immunology · 2025Article
- Evaluation of the Regulatory Effect of the Pan-PPAR Agonist Chiglitazar on the Dawn Phenomenon.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2025Article
253 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The nuclear receptor Rev-erbα regulates circadian rhythm and metabolism, but its effects are modest and it has been considered to be a secondary regulator of the cell-autonomous clock. Here we report that depletion of Rev-erbα together with closely related Rev-erbβ has dramatic effects on the cell-autonomous clock as well as hepatic lipid metabolism. Mouse embryonic fibroblasts were rendered arrhythmic by depletion of both Rev-erbs. In mouse livers, Rev-erbβ mRNA and protein levels oscillate with a diurnal pattern similar to that of Rev-erbα, and both Rev-erbs are recruited to a remarkably similar set of binding sites across the genome, enriched near metabolic genes. Depletion of both Rev-erbs in liver synergistically derepresses several metabolic genes as well as genes that control the positive limb of the molecular clock. Moreover, deficiency of both Rev-erbs causes marked hepatic steatosis, in contrast to relatively subtle changes upon loss of either subtype alone. These findings establish the two Rev-erbs as major regulators of both clock function and metabolism, displaying a level of subtype collaboration that is unusual among nuclear receptors but common among core clock proteins, protecting the organism from major perturbations in circadian and metabolic physiology.
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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.