ArticleMolecular cell2022
NSD1 mediates antagonism between SWI/SNF and polycomb complexes and is required for transcriptional activation upon EZH2 inhibition.
Article in Molecular cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Preclinical Anticipation of On- and Off-Target Resistance Mechanisms to Anti-Cancer Drugs: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- From single-site to pan-histone lysine mutagenesis in mammals.Nature genetics · 2026Article
- Identifying critical lysines in mammalian histone H3 with high-throughput CRISPR prime editing.Nature genetics · 2026Article
- Single cell CRISPR screen identifies antagonism between Nsd1-H3K36me2 and Ezh2-H3K27me3 orchestrates pluripotency transition.Stem cell reports · 2026Article
- Paediatric Therapeutic Development Workshop on rhabdoid tumours.British journal of cancer · 2026Review
- PHIP suppresses NuRD to enable the growth of SWI/SNF-mutant cancers.Nature communications · 2026Article
- Genomic and Immune Correlates of EZH2 Expression and Activity in Olfactory Neuroblastoma.Head & neck · 2026Article
- Histone 3 lysine 36 trimethylation by SETD2 shapes an epigenetic landscape in intestinal stem cells to orchestrate lipid metabolism and attenuate cell senescence.Cell death & disease · 2026Article
- H3K27me3-dependent imprinting and transcriptional regulation in early mouse embryos requires EZHIP-mediated restriction of PRC2 activity.Nature communications · 2026Article
- Many faces of mammalian NSD methyltransferases.Cellular & molecular biology letters · 2026Review
- Novel modifiers of oncoprotein-mediated Polycomb inhibition in Drosophila melanogaster.Genetics · 2025Article
- Therapeutic Targeting of Protein Lysine and Arginine Methyltransferases: Principles and Strategies for Inhibitor Design.International journal of molecular sciences · 2025Review
- The genetic basis of human height.Nature reviews. Genetics · 2025Review
- Investigating oncoprotein-mediated chromatin dysregulation inbioRxiv : the preprint server for biology · 2025Article
- Role of epigenetics in paediatric cancer pathogenesis & drug resistance.British journal of cancer · 2025Review
- The sotos syndrome gene Nsd1 safeguards developmental gene enhancers poised for transcription by maintaining the precise deposition of histone methylation.The Journal of biological chemistry · 2025Article
- Overgrowth-intellectual disability disorders: progress in biology, patient advocacy and innovative therapies.Disease models & mechanisms · 2025Review
- Rapid and robust validation of pooled CRISPR knockout screens using CelFi.Scientific reports · 2025Article
- Aberrant histone modifications in pediatric brain tumors.Frontiers in oncology · 2025Review
- The Role of SWI/SNF Complex in Bladder Cancer.Journal of cellular and molecular medicine · 2025Review
Corrections and comments
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Authors and funding
22 authors at 3 institutions in 1 country.
Funding
Abstract
Disruption of antagonism between SWI/SNF chromatin remodelers and polycomb repressor complexes drives the formation of numerous cancer types. Recently, an inhibitor of the polycomb protein EZH2 was approved for the treatment of a sarcoma mutant in the SWI/SNF subunit SMARCB1, but resistance occurs. Here, we performed CRISPR screens in SMARCB1-mutant rhabdoid tumor cells to identify genetic contributors to SWI/SNF-polycomb antagonism and potential resistance mechanisms. We found that loss of the H3K36 methyltransferase NSD1 caused resistance to EZH2 inhibition. We show that NSD1 antagonizes polycomb via cooperation with SWI/SNF and identify co-occurrence of NSD1 inactivation in SWI/SNF-defective cancers, indicating in vivo relevance. We demonstrate that H3K36me2 itself has an essential role in the activation of polycomb target genes as inhibition of the H3K36me2 demethylase KDM2A restores the efficacy of EZH2 inhibition in SWI/SNF-deficient cells lacking NSD1. Together our data expand the mechanistic understanding of SWI/SNF and polycomb interplay and identify NSD1 as the key for coordinating this transcriptional control.
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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.