ArticleProceedings of the National Academy of Sciences of the United States of America2017
Epithelial EZH2 serves as an epigenetic determinant in experimental colitis by inhibiting TNFα-mediated inflammation and apoptosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.
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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
75 citing papers in PubMed, 1 synthesis or guideline pooled it, 103 citations in OpenAlex.
- IBD-related inflammatory memory and colorectal cancer: epigenetic mechanisms and microbiome interventions.Frontiers in immunology · 2026Pooled it
- Butyrate epigenetically licenses sustained epithelial-T cell crosstalk for intestinal immune tolerance.Nature communications · 2026Article
- Different Immune Cells Modified With Chimeric Antigen Receptors Are Being Applied to Ovarian Cancer: Which Is the Most Effective?Cancer medicine · 2026Review
- Histone demethylase JMJD1A protects mice from enteric bacterial infection by upregulating CCL8 expression to recruit macrophages and CD4+ T cells.PLoS pathogens · 2026Article
- Epithelial MST1 deficiency promotes pyroptosis and aggravates inflammatory bowel disease via the YAP/p73 signaling pathway.Cell death and differentiation · 2026Article
- Long non-coding RNA STMN1P2 promotes breast cancer doxorubicin resistance by inhibiting pyroptosis through the hnRNPU-EZH2-TARF6-MALT1-caspase-1 pathway.Acta pharmacologica Sinica · 2026Article
- Molecular and Chromatin Accessibility Programs Underlying Epithelial Injury and Impaired Regeneration in Neonatal Necrotizing Enterocolitis.Cellular and molecular gastroenterology and hepatology · 2026Article
- TREM1 facilitates nonresponse to anti-TNF-α monoclonal antibodies in colitis via boosting ITCH/TAK1/caspase-8 axis-mediated macrophage pyroptosis.Journal of translational medicine · 2025Article
- Massive deciphering of the tissue nucleic acid-binding proteome via affinity chromatography integrated with data-independent acquisition-based proteomics.Nucleic acids research · 2025Article
- Review
- Nutraceutical Impact of Pumpkin Seed Oil on Expression Levels of EZH-2 and KRT-14 Genes against DSS-induced Inflammatory Bowel Disease in the Rat Model.Cell biochemistry and biophysics · 2025Article
- Accelerated biological aging and risk of inflammatory bowel disease: A prospective study from 401,013 participants.The journal of nutrition, health & aging · 2025Article
- Regulation of histone H3K27 methylation in inflammation and cancer.Molecular biomedicine · 2025Review
- Gasdermin E-mediated intestinal epithelial pyroptosis promotes chemically induced colitis in mice.Gastroenterology report · 2025Article
- Epithelial NSD2 maintains FMO-mediated taurine biosynthesis to prevent intestinal barrier disruption.Clinical and translational medicine · 2024Article
- Epigenetic aging of semen is associated with inflammation.Epigenetics · 2024Article
- Mesenchymal Stem Cells-Derived Exosomal miR-223-3p Alleviates Ocular Surface Damage and Inflammation by Downregulating Fbxw7 in Dry Eye Models.Investigative ophthalmology & visual science · 2024Article
- Deubiquitination of RIPK2 by OTUB2 augments NOD2 signalling and protective effects in intestinal inflammation.Clinical and translational medicine · 2024Article
- Telomere dysfunction alters intestinal stem cell dynamics to promote cancer.Developmental cell · 2024Article
- YAP represses intestinal inflammation through epigenetic silencing of JMJD3.Clinical epigenetics · 2024Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epithelial barrier disruption is a major cause of inflammatory bowel disease (IBD); however, the mechanism through which epigenetic regulation modulates intestinal epithelial integrity remains largely undefined. Here we show that EZH2, the catalytic subunit of polycomb repressive complex (PRC2), is indispensable for maintaining epithelial cell barrier integrity and homeostasis under inflammatory conditions. In accordance with reduced EZH2 expression in patients, the inactivation of EZH2 in IECs sensitizes mice to DSS- and TNBS-induced experimental colitis. Conversely, EZH2 overexpression in the intestinal epithelium renders mice more resistant to colitis. Mechanistically, the genes encoding TRAF2/5 are held in a finely tuned bivalent status under inflammatory conditions. EZH2 deficiency potentiates the expression of these genes to enhance TNFα-induced NF-κB signaling, thereby leading to uncontrolled inflammation. More importantly, we show that EZH2 depletion compromises the protective role of NF-κB signaling in cell survival by directly up-regulating ITCH, a well-known E3 ligase that degrades the c-FLIP protein. Thus, our findings highlight an epigenetic mechanism by which EZH2 integrates the multifaceted effects of TNFα signaling to promote the inflammatory response and apoptosis in colitis.
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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.