ArticleNucleic acids research2022
FACT subunit SUPT16H associates with BRD4 and contributes to silencing of interferon signaling.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 18 citations in OpenAlex.
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- The extra-terminal domain drives the role of BET proteins in transcription.Nucleic acids research · 2026Article
- Unraveling the layers of epigenetic control in respiratory antiviral defense.Journal of virology · 2026Review
- The FACT complex associates with the RPA complex at viral replication compartments to promote adenovirus infection.Journal of virology · 2026Article
- A pan-viral map of host dependency factors from multi-omics integration and machine learning across influenza A, SARS-CoV-2, Zika, and dengue viruses.Journal of translational medicine · 2026Article
- Inhibition of KDM5A/B promotes antitumor innate immune responses in HHV-8/KSHV-positive B-cell lymphomas.bioRxiv : the preprint server for biology · 2026Article
- Altered histone modifications in Aedes aegypti midguts following Rift Valley fever virus exposure.Scientific reports · 2026Article
- Insights into FACT in Cancers with Targeted Therapeutic Implications.Molecular and cellular biology · 2026Review
- BRD4 inhibition suppresses histone H4 UFMylation to increase ferroptosis sensitivity through TXNIP.Cell death & disease · 2025Article
- Analysis of the Porcine Reproductive and Respiratory Syndrome Virus Nucleocapsid Interactome.Journal of proteome research · 2025Article
- Altered histone modifications inbioRxiv : the preprint server for biology · 2025Article
- Molecular mechanisms of thymopoietin in papillary thyroid cancer: Multiplatform gene expression data, gene knockout screening, and in-house immunohistochemistry.World journal of clinical oncology · 2025Article
- Immuno-epigenetic paradigms in coronavirus infection.Frontiers in immunology · 2025Review
- Review
- Insights into the Mechanism of Curaxin CBL0137 Epigenetic Activity: The Induction of DNA Demethylation and the Suppression of BET Family Proteins.International journal of molecular sciences · 2023Article
- Relevance of BET Family Proteins in SARS-CoV-2 Infection.Biomolecules · 2021Review
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11 authors at 3 institutions in 1 country.
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Abstract
FACT (FAcilitates Chromatin Transcription) is a heterodimeric protein complex composed of SUPT16H and SSRP1, and a histone chaperone participating in chromatin remodeling during gene transcription. FACT complex is profoundly regulated, and contributes to both gene activation and suppression. Here we reported that SUPT16H, a subunit of FACT, is acetylated in both epithelial and natural killer (NK) cells. The histone acetyltransferase TIP60 contributes to the acetylation of SUPT16H middle domain (MD) at lysine 674 (K674). Such acetylation of SUPT16H is recognized by bromodomain protein BRD4, which promotes protein stability of SUPT16H in both epithelial and NK cells. We further demonstrated that SUPT16H-BRD4 associates with histone modification enzymes (HDAC1, EZH2), and further regulates their activation status and/or promoter association as well as affects the relevant histone marks (H3ac, H3K9me3 and H3K27me3). BRD4 is known to profoundly regulate interferon (IFN) signaling, while such function of SUPT16H has never been explored. Surprisingly, our results revealed that SUPT16H genetic knockdown via RNAi or pharmacological inhibition by using its inhibitor, curaxin 137 (CBL0137), results in the induction of IFNs and interferon-stimulated genes (ISGs). Through this mechanism, depletion or inhibition of SUPT16H is shown to efficiently inhibit infection of multiple viruses, including Zika, influenza, and SARS-CoV-2. Furthermore, we demonstrated that depletion or inhibition of SUPT16H also causes the remarkable activation of IFN signaling in NK cells, which promotes the NK-mediated killing of virus-infected cells in a co-culture system using human primary NK cells. Overall, our studies unraveled the previously un-appreciated role of FACT complex in coordinating with BRD4 and regulating IFN signaling in both epithelial and NK cells, and also proposed the novel application of the FACT inhibitor CBL0137 to treat viral infections.
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