ArticleProceedings of the National Academy of Sciences of the United States of America2012
Nuclear factor-κB binding motifs specify Toll-like receptor-induced gene repression through an inducible repressosome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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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
45 citing papers in PubMed, 77 citations in OpenAlex.
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- Epigenetic mechanisms of inflammatory memory in the central nervous system.Nature immunology · 2026Review
- NCOR2 represses MHC class I molecule expression to drive metastatic progression of breast cancer.Nature communications · 2026Article
- Trawling the depths of gene regulation: transcription-factor families orchestrating immunity in teleost fish.Frontiers in immunology · 2026Review
- Interferons and epigenetic mechanisms in training, priming and tolerance of monocytes and hematopoietic progenitors.Immunological reviews · 2024Review
- Epigenetic regulation of innate immune dynamics during inflammation.Journal of leukocyte biology · 2024Review
- Altered DNA methylation underlies monocyte dysregulation and immune exhaustion memory in sepsis.Cell reports · 2024Article
- Inhibition of specific signaling pathways rather than epigenetic silencing of effector genes is the leading mechanism of innate tolerance.Frontiers in immunology · 2023Article
- Screening of organoids derived from patients with breast cancer implicates the repressor NCOR2 in cytotoxic stress response and antitumor immunity.Nature cancer · 2022Article
- Bcl-3: A Double-Edged Sword in Immune Cells and Inflammation.Frontiers in immunology · 2022Review
- Recent insights intoEpigenetics · 2021Review
- PARP Traps Rescue the Pro-Inflammatory Response of Human Macrophages in the In Vitro Model of LPS-Induced Tolerance.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Reversing Post-Infectious Epigenetic-Mediated Immune Suppression.Frontiers in immunology · 2021Review
- Lactylation, a Novel Metabolic Reprogramming Code: Current Status and Prospects.Frontiers in immunology · 2021Review
- Article
- HDAC3 ensures stepwise epidermal stratification via NCoR/SMRT-reliant mechanisms independent of its histone deacetylase activity.Genes & development · 2020Article
- Histamine-mediated autocrine signaling in mesenteric perilymphatic mast cells.American journal of physiology. Regulatory, integrative and comparative physiology · 2020Article
- Diversity, Mechanisms, and Significance of Macrophage Plasticity.Annual review of pathology · 2020Review
- HDAC3 Mediates the Inflammatory Response and LPS Tolerance in Human Monocytes and Macrophages.Frontiers in immunology · 2020Article
- Epigenetic regulation of macrophages: from homeostasis maintenance to host defense.Cellular & molecular immunology · 2020Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Sustained Toll-like receptor (TLR) stimulation continuously activates antimicrobial genes but paradoxically represses inflammatory genes. This phenomenon, termed TLR tolerance, is essential for preventing fatal inflammatory conditions such as sepsis, but its underlying mechanisms are unclear. We report here that NF-κB binding nucleic acids of gene promoters are tolerogenic motifs, which selectively recruit an NcoR-Hdac3-deacetylated-p50 repressosome to inflammatory genes. Genome-wide analyses of TLR4-induced genes revealed that NF-κB motifs were the only regulatory elements significantly enriched in tolerizable genes. Mutating the NF-κB motifs of tolerizable genes converted them into nontolerizable ones, whereas inserting NF-κB binding motifs into nontolerizable genes conferred the tolerance. Although NF-κB p50 was essential for assembling the repressosome, genetic disruption of the NcoR-Hdac3 interaction alone was sufficient to completely abolish TLR4 tolerance and to render mice vulnerable to sepsis. Thus, the specificity of TLR tolerance is dictated by evolutionally conserved nucleic acid motifs that bound by NF-κB and the NcoR repressosome.
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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.