ArticleThe Journal of biological chemistry2015
Mechanistic analysis of the role of bromodomain-containing protein 4 (BRD4) in BRD4-NUT oncoprotein-induced transcriptional activation.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 70 citations in OpenAlex.
- NSD3 stabilizes nuclear compartmentalization and promotes megabase-scale chromatin interactions.bioRxiv : the preprint server for biology · 2026Article
- Advancing Understanding and Therapeutic Strategies for NUT Sarcomas: Comprehensive Review of the Literature and Two Cases.Journal of immunotherapy and precision oncology · 2025Review
- Pulmonary NUT carcinoma, an elusive and refractory entity, shows transient response to chemotherapeutics and PD-1 inhibitor: a case report and literature review.Frontiers in immunology · 2025Review
- Molecular and clinicopathologic characteristics of CNS embryonal tumors with BRD4::LEUTX fusion.Acta neuropathologica communications · 2024Article
- Molecular features driving condensate formation and gene expression by the BRD4-NUT fusion oncoprotein are overlapping but distinct.Scientific reports · 2023Article
- Cell state-dependent chromatin targeting in NUT carcinoma.Genetics · 2023Article
- Molecular features driving condensate formation and gene expression by the BRD4-NUT fusion oncoprotein are overlapping but distinct.bioRxiv : the preprint server for biology · 2023Article
- Cell state-dependent chromatin targeting in NUT carcinoma.bioRxiv : the preprint server for biology · 2023Article
- BET Bromodomain Inhibitors: Novel Design Strategies and Therapeutic Applications.Molecules (Basel, Switzerland) · 2023Review
- Structural mechanism of BRD4-NUT and p300 bipartite interaction in propagating aberrant gene transcription in chromatin in NUT carcinoma.Nature communications · 2023Article
- Histone Readers and Their Roles in Cancer.Cancer treatment and research · 2023Article
- Structural insights into p300 regulation and acetylation-dependent genome organisation.Nature communications · 2022Article
- NUT Carcinoma: Clinicopathologic Features, Molecular Genetics and Epigenetics.Frontiers in oncology · 2022Review
- Review
- Chemical Screen Identifies Diverse and Novel Histone Deacetylase Inhibitors as Repressors of NUT Function: Implications for NUT Carcinoma Pathogenesis and Treatment.Molecular cancer research : MCR · 2021Article
- Clinicopathological and molecular characterizations of pulmonary NUT midline carcinoma.Cancer medicine · 2021Article
- Supercharging BRD4 with NUT in carcinoma.Oncogene · 2021Review
- Immunotherapy and Targeting the Tumor Microenvironment: Current Place and New Insights in Primary Pulmonary NUT Carcinoma.Frontiers in oncology · 2021Review
- Combined Targeting of the BRD4-NUT-p300 Axis in NUT Midline Carcinoma by Dual Selective Bromodomain Inhibitor, NEO2734.Molecular cancer therapeutics · 2020Article
- Article
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2 authors at 1 institution in 1 country.
Funding
Abstract
NUT midline carcinoma (NMC) is a rare but highly aggressive cancer typically caused by the translocation t(15;19), which results in the formation of the BRD4-NUT fusion oncoprotein. Previous studies have demonstrated that fusion of the NUT protein with the double bromodomains of BRD4 may significantly alter the cellular gene expression profile to contribute to NMC tumorigenesis. However, the mechanistic details of this BRD4-NUT function remain poorly understood. In this study, we examined the NUT function in transcriptional regulation by targeting it to a LacO transgene array integrated in U2OS 2-6-3 cells, which allow us to visualize how NUT alters the in situ gene transcription dynamic. Using this system, we demonstrated that the NUT protein tethered to the LacO locus recruits p300/CREB-binding protein (CBP), induces histone hyperacetylation, and enriches BRD4 to the transgene array chromatin foci. We also discovered that, in BRD4-NUT expressed in NMC cells, the NUT moiety of the fusion protein anchored to chromatin by the double bromodomains also stimulates histone hyperacetylation, which causes BRD4 to bind tighter to chromatin. Consequently, multiple BRD4-interacting factors are recruited to the NUT-associated chromatin locus to activate in situ transgene expression. This gene transcription function was repressed by either expression of a dominant negative inhibitor of the p300-NUT interaction or treatment with (+)-JQ1, which dissociates BRD4 from the LacO chromatin locus. Our data support a model in which BRD4-NUT-stimulated histone hyperacetylation recruits additional BRD4 and interacting partners to support transcriptional activation, which underlies the BRD4-NUT oncogenic mechanism in NMC.
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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.