ArticleGastroenterology2023
Loss of SUV420H2-Dependent Chromatin Compaction Drives Right-Sided Colon Cancer Progression.
Article in Gastroenterology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- The role of R-loops-mediated epigenetic regulation in genome stability maintenance and disease pathogenesis: a systematic review.Epigenetics · 2026Pooled it
- Article
- Histone H4 lysine 20 tri-methylation safeguards breast cancer lineage fidelity and unfolded protein response.Nature communications · 2026Article
- Epigenetics in lung cancer precision medicine: from bench to bedside-a narrative review.Translational lung cancer research · 2026Review
- KMT5C-H4K20me3 drives changes in epigenetic landscape independent of H3K9me3.bioRxiv : the preprint server for biology · 2026Article
- Evaluation of targeted and immune combination therapies in a rat model of hormone receptor-positive breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Review
- DNA, RNA, and histone methylation regulation enzymes and their crosstalk in colorectal carcinogenesis and progression: a review of molecular mechanisms, clinical implications, and future perspectives.Cellular & molecular biology letters · 2025Review
- Spatial Proteomic Analysis Highlights Molecular Reprogramming in Optic Nerve Invasive Retinoblastoma.Investigative ophthalmology & visual science · 2025Article
- The LncRNA STEAP3-AS1 promotes liver metastasis in colorectal cancer by regulating histone lactylation through chromatin remodelling.Journal of experimental & clinical cancer research : CR · 2025Article
- Multi-omics in colorectal cancer liver metastasis: applications and research advances.Cancer biology & medicine · 2025Review
- Does side matter? Deciphering mechanisms that underpin side-dependent pathogenesis and therapy response in colorectal cancer.Molecular cancer · 2025Review
- Targeting KMT5C Suppresses Lung Cancer Progression and Enhances the Efficacy of Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Lyn/RUVBL1 Complex Promotes Colorectal Cancer Liver Metastasis by Regulating Arachidonic Acid Metabolism Through Chromatin Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Chromatin accessibility: biological functions, molecular mechanisms and therapeutic application.Signal transduction and targeted therapy · 2024Review
- Epigenetic reprogramming in gastrointestinal cancer: biology and translational perspectives.MedComm · 2024Review
- Molecular subtypes of colorectal cancer in the era of precision oncotherapy: Current inspirations and future challenges.Cancer medicine · 2024Review
- Impact of Histone Lysine Methyltransferase SUV4-20H2 on Cancer Onset and Progression with Therapeutic Potential.International journal of molecular sciences · 2024Review
- The application of organoids in colorectal diseases.Frontiers in pharmacology · 2024Review
- Intestinal organoid modeling: bridging the gap from experimental model to clinical translation.Frontiers in oncology · 2024Review
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsEpigenetic processes regulating gene expression contribute markedly to epithelial cell plasticity in colorectal carcinogenesis. The lysine methyltransferase SUV420H2 comprises an important regulator of epithelial plasticity and is primarily responsible for trimethylation of H4K20 (H4K20me3). Loss of H4K20me3 has been suggested as a hallmark of human cancer due to its interaction with DNMT1. However, the role of Suv4-20h2 in colorectal cancer is unknown.
methodsWe examined the alterations in histone modifications in patient-derived colorectal cancer organoids. Patient-derived colorectal cancer organoids and mouse intestinal organoids were genetically manipulated for functional studies in patient-derived xenograft and orthotopic transplantation. Gene expression profiling, micrococcal nuclease assay, and chromatin immunoprecipitation were performed to understand epigenetic regulation of chromatin states and gene expression in patient-derived and mouse intestinal organoids.
resultsWe found that reduced H4K20me3 levels occurred predominantly in right-sided patient-derived colorectal cancer organoids, which were associated with increased chromatin accessibility. Re-compaction of chromatin by methylstat, a histone demethylase inhibitor, resulted in reduced growth selectively in subcutaneously grown tumors derived from right-sided cancers. Using mouse intestinal organoids, we confirmed that Suv4-20h2-mediated H4K20me3 is required for maintaining heterochromatin compaction and to prevent R-loop formation. Cross-species comparison of Suv4-20h2-depleted murine organoids with right-sided colorectal cancer organoids revealed a large overlap of gene signatures involved in chromatin silencing, DNA methylation, and stemness/Wnt signaling.
conclusionsLoss of Suv4-20h2-mediated H4K20me3 drives right-sided colorectal tumorigenesis through an epigenetically controlled mechanism of chromatin compaction. Our findings unravel a conceptually novel approach for subtype-specific therapy of this aggressive form of colorectal cancer.
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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.