ArticleScience advances2019
A novel P300 inhibitor reverses DUX4-mediated global histone H3 hyperacetylation, target gene expression, and cell death.
Article in Science advances, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 67 citations in OpenAlex.
- Undifferentiated round cell sarcoma with CIC::NUTM1 fusion: expanding the clinicopathologic spectrum of a rare molecular variant of CIC-rearranged sarcoma.Virchows Archiv : an international journal of pathology · 2026Article
- Article
- The EP300-Targeting Drug CCS1477 Inhibits the Growth and Development of Diffuse Large B-Cell Lymphoma by Promoting Apoptosis and Mitophagy to Reduce Drug Resistance.Anti-cancer agents in medicinal chemistry · 2026Article
- Modeling CIC::DUX4 sarcoma reveals oncogene-mediated MHCI-dependent immune evasion.Molecular cancer · 2025Article
- AAV-shDUX4 provides short-term benefits but limited long-term efficacy in a DUX4 mouse model of FSHD.Molecular therapy. Methods & clinical development · 2025Article
- Iron supplementation alleviates pathologies in a mouse model of facioscapulohumeral muscular dystrophy.The Journal of clinical investigation · 2025Article
- DUX4 at 25: how it emerged from "junk DNA" to become the cause of facioscapulohumeral muscular dystrophy.Skeletal muscle · 2025Review
- The recent clinical trial of losmapimod for the treatment of facioscapulohumeral muscular dystrophy.Neuromuscular disorders : NMD · 2025Review
- Embryonic Origins of Cancer: Insights from Double Homeobox 4 Regulation.Biomolecules · 2025Review
- The Functions and Regulatory Mechanisms of Histone Modifications in Skeletal Muscle Development and Disease.International journal of molecular sciences · 2025Review
- The important role of the histone acetyltransferases p300/CBP in cancer and the promising anticancer effects of p300/CBP inhibitors.Cell biology and toxicology · 2025Review
- Muscular Dystrophies.Advances in experimental medicine and biology · 2025Review
- CBP/p300 lysine acetyltransferases inhibit HIV-1 expression in latently infected T cells.iScience · 2024Article
- The impact of retrotransposons on zygotic genome activation and the chromatin landscape of early embryos.Annals of the New York Academy of Sciences · 2024Review
- Pharmacological targeting of P300/CBP reveals EWS::FLI1-mediated senescence evasion in Ewing sarcoma.Molecular cancer · 2024Article
- Antagonism among DUX family members evolved from an ancestral toxic single homeodomain protein.iScience · 2023Article
- Comparative Analysis of Drug-like EP300/CREBBP Acetyltransferase Inhibitors.ACS chemical biology · 2023Article
- Pharmacotherapeutic Approaches to Treatment of Muscular Dystrophies.Biomolecules · 2023Review
- WDR5 is required for DUX4 expression and its pathological effects in FSHD muscular dystrophy.Nucleic acids research · 2023Article
- Influence ofInternational journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Facioscapulohumeral muscular dystrophy (FSHD) results from mutations causing overexpression of the transcription factor, DUX4, which interacts with the histone acetyltransferases, EP300 and CBP. We describe the activity of a new spirocyclic EP300/CBP inhibitor, iP300w, which inhibits the cytotoxicity of the DUX4 protein and reverses the overexpression of most DUX4 target genes, in engineered cell lines and FSHD myoblasts, as well as in an FSHD animal model. In evaluating the effect of iP300w on global histone H3 acetylation, we discovered that DUX4 overexpression leads to a dramatic global increase in the total amount of acetylated histone H3. This unexpected effect requires the C-terminus of DUX4, is conserved with mouse Dux, and may facilitate zygotic genome activation. This global increase in histone H3 acetylation is reversed by iP300w, highlighting the central role of EP300 and CBP in the transcriptional mechanism underlying DUX4 cytotoxicity and the translational potential of blocking this interaction.
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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.