ArticleEpigenetics & chromatin2019
Tat inhibition by didehydro-Cortistatin A promotes heterochromatin formation at the HIV-1 long terminal repeat.
Article in Epigenetics & chromatin, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 77 citations in OpenAlex.
- Discovery of CDK8/19 inhibitors as lead compounds for IL-6-dependent lymphoma enabled by the formal synthesis of cortistatin A.Science advances · 2026Article
- Quantitative limits of host-driven HIV transcription and host gene control by the viral transactivator Tat.Nucleic acids research · 2026Article
- Review
- Breaking into HIV-1's Epigenetic Vault: Cure Strategies to Eliminate the Viral Reservoir.Viruses · 2026Review
- Tools to Quantify and Characterize the Persistent Reservoir in People with HIV-1: Focus on Non-B Subtypes.Viruses · 2026Review
- The human chromatin remodeling complex p400 restricts HIV-1 transcription in a Tat-dependent manner.Nucleic acids research · 2025Article
- The RNA-binding protein RBM39 scaffolds an m⁶A-dependent RNA decay complex that destabilizes Tat transcripts and restricts HIV-1 reactivation.PLoS biology · 2025Article
- Lymphoid and CXCR4 Cell Targeted Lipid Nanoparticles Facilitate HIV-1 Proviral DNA Excision.Advanced healthcare materials · 2025Article
- The p400 complex promotes HIV-1 latency by suppressing viral transcription and altering the host cell state.Nucleic acids research · 2025Article
- Harnessing antiviral RNAi therapeutics for pandemic viruses: SARS-CoV-2 and HIV.Drug delivery and translational research · 2025Review
- In vitro HIV DNA integration in STAT3 drives T cell persistence-A model of HIV-associated T cell lymphoma.PLoS pathogens · 2025Article
- HIV-1 Tat: Molecular Switch in Viral Persistence and Emerging Technologies for Functional Cure.International journal of molecular sciences · 2025Review
- FUBP3 enhances HIV-1 transcriptional activity and regulates immune response pathways in T cells.Molecular therapy. Nucleic acids · 2025Article
- Suppression of HIV-1 transcription and latency reversal via ectopic expression of the viral antisense transcript AST.Science advances · 2025Article
- BRD4 modulator ZL0580 and LEDGINs additively block and lock HIV-1 transcription.Nature communications · 2025Article
- Human chromatin remodelers regulating HIV-1 transcription: a target for small molecule inhibitors.Epigenetics & chromatin · 2025Review
- Heat shock protein 90 is a chaperone regulator of HIV-1 latency.PLoS pathogens · 2025Article
- The Complex Interactions Between HIV-1 and Human Host Cell Genome: From Molecular Mechanisms to Clinical Practice.International journal of molecular sciences · 2025Review
- The HIV-1 Transcriptional Program: From Initiation to Elongation Control.Journal of molecular biology · 2025Review
- HIV and the gut: implications for HIV persistence, immune dysfunction and cure strategies.Frontiers in immunology · 2025Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundTranscription from the integrated HIV-1 promoter is directly governed by its chromatin environment, and the nucleosome-1 downstream from the transcription start site directly impedes transcription from the HIV-1 promoter. The HIV-1 Tat protein regulates the passage from viral latency to active transcription by binding to the viral mRNA hairpin (TAR) and recruiting transcriptional factors to promote transcriptional elongation. The Tat inhibitor didehydro-Cortistatin A (dCA) inhibits transcription and overtime, the lack of low-grade transcriptional events, triggers epigenetic changes at the latent loci that "lock" HIV transcription in a latent state.
resultsHere we investigated those epigenetic changes using multiple cell line models of HIV-1 latency and active transcription. We demonstrated that dCA treatment does not alter the classic nucleosome positioning at the HIV-1 promoter, but promotes tighter nucleosome/DNA association correlating with increased deacetylated H3 occupancy at nucleosome-1. Recruitment of the SWI/SNF chromatin remodeling complex PBAF, necessary for Tat-mediated transactivation, is also inhibited, while recruitment of the repressive BAF complex is enhanced. These results were supported by loss of RNA polymerase II recruitment on the HIV genome, even during strong stimulation with latency-reversing agents. No epigenetic changes were detected in cell line models of latency with Tat-TAR incompetent proviruses confirming the specificity of dCA for Tat.
conclusionsWe characterized the dCA-mediated epigenetic signature on the HIV genome, which translates into potent blocking effects on HIV expression, further strengthening the potential of Tat inhibitors in "block-and-lock" functional cure approaches.
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