ArticleNature structural & molecular biology2007
Identification of heme as the ligand for the orphan nuclear receptors REV-ERBalpha and REV-ERBbeta.
Article in Nature structural & molecular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 324 papers.
What it found
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Who cites it
324 citing papers in PubMed, 551 citations in OpenAlex.
- Rev-Erb co-regulates muscle regeneration via tethered interaction with the NF-Y cistrome.Molecular metabolism · 2017Trial
- Time matters: circadian genetics and the molecular logic of human health and disease.Nature reviews. Genetics · 2026Review
- Rev-erb-α in Skeletal Muscle Adaptation: Integrating Circadian Control Mechanisms and Exercise Dynamic Responses.Journal of cellular physiology · 2026Review
- The circadian architecture of tumor immunity: mechanistic insights and treatment strategies.Biomarker research · 2026Review
- The Yeast Metabolic Cycle as a Tractable Cellular Framework for Redox Timing, Redox Buffering, and Transcriptome Fidelity.Antioxidants (Basel, Switzerland) · 2026Article
- Multilevel transcriptional regulation of embryonic sex determination and dosage compensation by the X-signal element sex-1.Genetics · 2026Article
- Stomach at the crossroads: nuclear receptor signaling at the interface between what we are and what we eat.Physiological reviews · 2026Review
- The Circadian-Light-Hygiene Hypothesis: A Potential Modulator of Fertility and Birthrate Trends.Biology · 2026Review
- Advances in research on circadian rhythms and colorectal cancer.BMC medical genomics · 2026Review
- HR3/RORα-mediated cholesterol sensing regulates TOR signaling.Nature communications · 2026Article
- A review of the circadian regulation of stem cells: harnessing the internal body clock for enhanced regenerative therapies.Stem cell research & therapy · 2026Review
- The Small Molecule SR8278 Inhibits Cell Proliferation Independent of the REV-ERB Nuclear Receptor Proteins in Human Keratinocytes.Biomolecules · 2026Article
- Chronic intermittent hypoxia reshapes circadian metabolic architecture in a model of sleep apnea.Science advances · 2026Article
- Heme and CO metabolism by the canonical human heme oxygenases.Journal of inorganic biochemistry · 2026Review
- Negative regulation of TbioRxiv : the preprint server for biology · 2026Article
- Targeting metabolic vulnerabilities: REV-ERB agonist SR9009 potentiates sorafenib efficacy in liver cancer.Cell death discovery · 2026Article
- The Role of BMAL1 in Regulating Circadian Rhythms During Airway Remodeling in Asthma.Journal of immunology research · 2026Review
- Article
- Haematometabolism rewiring in atherosclerotic cardiovascular disease.Nature reviews. Cardiology · 2025Review
- Circadian clock genes and cell survival in bipolar disorder: Insights into lithium responsiveness and molecular mechanisms in patient-derived neural progenitor cells and mouse neurons.The FEBS journal · 2025Article
264 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The nuclear receptors REV-ERBalpha (encoded by NR1D1) and REV-ERBbeta (NR1D2) have remained orphans owing to the lack of identified physiological ligands. Here we show that heme is a physiological ligand of both receptors. Heme associates with the ligand-binding domains of the REV-ERB receptors with a 1:1 stoichiometry and enhances the thermal stability of the proteins. Results from experiments of heme depletion in mammalian cells indicate that heme binding to REV-ERB causes the recruitment of the co-repressor NCoR, leading to repression of target genes including BMAL1 (official symbol ARNTL), an essential component of the circadian oscillator. Heme extends the known types of ligands used by the human nuclear receptor family beyond the endocrine hormones and dietary lipids described so far. Our results further indicate that heme regulation of REV-ERBs may link the control of metabolism and the mammalian clock.
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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.