ArticleMolecular cell2015
NSD3-Short Is an Adaptor Protein that Couples BRD4 to the CHD8 Chromatin Remodeler.
Article in Molecular cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
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Who cites it
104 citing papers in PubMed, 157 citations in OpenAlex.
- NSD Histone Methyltransferases in Solid Tumors: Biological Functions, Oncogenic Mechanisms and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- BRD4: From molecular understanding to therapeutics development.Molecular cell · 2026Review
- The histone methyltransferase NSD3 oncogene triggers ribosomal DNA transcription, interfering with FOSL2 in cancer.Cell death & disease · 2026Article
- Tandem bromodomains of BRD4 cooperatively read poly-acetylated nucleosomes to enhance chromatin engagement and regulate breast cancer phenotypes.bioRxiv : the preprint server for biology · 2026Article
- Recruitment of BRD4 to the ASXL1 genomic targets depends on the extra-terminal domain of BRD4.Nature communications · 2026Article
- NSD3 stabilizes nuclear compartmentalization and promotes megabase-scale chromatin interactions.bioRxiv : the preprint server for biology · 2026Article
- Cocaine-Induced Changes in the BRD4 Interactome Identifies Casein Kinase 1 Epsilon as a Therapeutic Target.Journal of neurochemistry · 2026Article
- H3K36 Methylation as a Guardian of Epigenome Integrity.Nature communications · 2025Article
- NSD Family-Mediated H3K36 Methylation in Human Cancer: Mechanisms and Therapeutic Opportunities.Biomedicines · 2025Review
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- Isoform-specific function of NSD3 in DNA replication stress confers resistance to PARP inhibitors in prostate cancer.Molecular cell · 2025Article
- A specific form of cPRC1 containing CBX4 is co-opted to mediate oncogenic gene repression in diffuse midline glioma.Molecular cell · 2025Article
- A CHD8-TRRAP axis facilitates MYC and E2F target gene regulation in human neural stem cells.iScience · 2025Article
- NSD3 protein methylation and stabilization transforms human ES cells into variant state.Life science alliance · 2025Article
- Targeting lysine acetylation readers and writers.Nature reviews. Drug discovery · 2025Review
- Epigenetic therapies targeting histone lysine methylation: complex mechanisms and clinical challenges.The Journal of clinical investigation · 2024Review
- Systematic perturbations of SETD2, NSD1, NSD2, NSD3, and ASH1L reveal their distinct contributions to H3K36 methylation.Genome biology · 2024Article
- NSD3 in Cancer: Unraveling Methyltransferase-Dependent and Isoform-Specific Functions.International journal of molecular sciences · 2024Review
- The chromatin signatures of enhancers and their dynamic regulation.Nucleus (Austin, Tex.) · 2023Review
- PROTACs Targeting Epigenetic Proteins.Acta materia medica · 2023Article
44 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 2 countries.
Funding
Abstract
The bromodomain and extraterminal (BET) protein BRD4 is a therapeutic target in acute myeloid leukemia (AML). Here, we demonstrate that the AML maintenance function of BRD4 requires its interaction with NSD3, which belongs to a subfamily of H3K36 methyltransferases. Unexpectedly, AML cells were found to only require a short isoform of NSD3 that lacks the methyltransferase domain. We show that NSD3-short is an adaptor protein that sustains leukemia by linking BRD4 to the CHD8 chromatin remodeler, by using a PWWP chromatin reader module, and by employing an acidic transactivation domain. Genetic targeting of NSD3 or CHD8 mimics the phenotypic and transcriptional effects of BRD4 inhibition. Furthermore, BRD4, NSD3, and CHD8 colocalize across the AML genome, and each is released from super-enhancer regions upon chemical inhibition of BET bromodomains. These findings suggest that BET inhibitors exert therapeutic effects in leukemia by evicting BRD4-NSD3-CHD8 complexes from chromatin to suppress transcription.
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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.