ArticleNature communications2023
Structural mechanism of BRD4-NUT and p300 bipartite interaction in propagating aberrant gene transcription in chromatin in NUT carcinoma.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 40 citations in OpenAlex.
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- Targeting fusion proteins in solid tumors: from oncogenic mechanisms to clinical interventions.Acta pharmacologica Sinica · 2026Review
- Histone modification cross-talk: analytical tools and molecular mechanisms.The Biochemical journal · 2026Review
- Modeling of Capicua Family Fusion Oncoprotein-Driven Cancers Reveals Gene-Specific Functionality.Molecular cancer research : MCR · 2026Article
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- Pharmacological targeting of oncogenic condensates in cancer: mechanistic insights and therapeutic opportunities.Acta pharmacologica Sinica · 2026Review
- 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
- Cell death modulation dictates tissue-specific tropism of lumpy skin disease virus.PLoS pathogens · 2026Article
- BRD2 bridges TFIID and MOF-H4K16ac-containing nucleosomes to promote transcriptional initiation.Molecular cell · 2026Article
- Deregulated enhancer-promoter communication in cancer through altered nuclear architecture.International journal of cancer · 2026Review
- Fusion oncoproteins orchestrate tumorigenesis and sustain malignant progression via a positive feedback mechanism.Cell & bioscience · 2026Review
- p300: expanding beyond acetylation to mastermind lactylation-dependent tumorigenesis.Frontiers in cell and developmental biology · 2026Review
- Acetyl-CoA carboxylase 1 knockdown promotes esophageal squamous cell carcinoma metastasis via the CXCL8-NET axis.Communications biology · 2025Article
- A Novel EP300 Variant in an African American Girl With Global Developmental Delay and Leukemia.Molecular genetics & genomic medicine · 2025Article
- Phase Separation in Chromatin Organization and Human Diseases.International journal of molecular sciences · 2025Review
- Transcription regulation by biomolecular condensates.Nature reviews. Molecular cell biology · 2025Review
- Review
- Targeting lysine acetylation readers and writers.Nature reviews. Drug discovery · 2025Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
BRD4-NUT, a driver fusion mutant in rare and highly aggressive NUT carcinoma, acts in aberrant transcription of anti-differentiation genes by recruiting histone acetyltransferase (HAT) p300 and promoting p300-driven histone hyperacetylation and nuclear condensation in chromatin. However, the molecular basis of how BRD4-NUT recruits and activates p300 remains elusive. Here, we report that BRD4-NUT contains two transactivation domains (TADs) in NUT that bind to the TAZ2 domain in p300. Our NMR structures reveal that NUT TADs adopt amphipathic helices when bound to the four-helical bundle TAZ2 domain. The NUT protein forms liquid-like droplets in-vitro that are enhanced by TAZ2 binding in 1:2 stoichiometry. The TAD/TAZ2 bipartite binding in BRD4-NUT/p300 triggers allosteric activation of p300 and acetylation-driven liquid-like condensation on chromatin that comprise histone H3 lysine 27 and 18 acetylation and transcription proteins BRD4L/S, CDK9, MED1, and RNA polymerase II. The BRD4-NUT/p300 chromatin condensation is key for activating transcription of pro-proliferation genes such as ALX1, resulting ALX1/Snail signaling and epithelial-to-mesenchymal transition. Our study provides a previously underappreciated structural mechanism illuminating BRD4-NUT's bipartite p300 recruitment and activation in NUT carcinoma that nucleates a feed-forward loop for propagating histone hyperacetylation and chromatin condensation to sustain aberrant anti-differentiation gene transcription and perpetual tumor cell growth.
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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.