ArticleThe Journal of clinical investigation2018
HIV latency is reversed by ACSS2-driven histone crotonylation.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
99 citing papers in PubMed, 164 citations in OpenAlex.
- Disruption of latent HIV in vivo during the clearance of actinic keratosis by ingenol mebutate.JCI insight · 2019Trial
- DHRS9 generates crotonyl-CoA from butyryl-CoA to epigenetically regulate STING transcription and potentiate immune activation.Cell death and differentiation · 2026Article
- Coming to light: the transcriptional regulatory roles of histone lysine crotonylation in health and disease.Cellular & molecular biology letters · 2026Review
- Histone Modifications in Cardiovascular Disease: Mechanisms and Therapeutic Opportunities.MedComm · 2026Review
- CPT1B K321 crotonylation contributes to cardiac dysfunction in endotoxic shock.Experimental & molecular medicine · 2026Article
- Histone decrotonylation plays a distinct role in HIV latency.Science advances · 2026Article
- Fueling silence: Metabolic control of latent viral infection.PLoS pathogens · 2026Article
- ACSS2-mediated lysine crotonylation attenuates senescence and enhances the therapeutic efficacy of adipose-derived stem cells in inflammatory bowel disease.Cell regeneration (London, England) · 2026Article
- Epigenetic mechanisms of retroviral regulation: a comparative review.Epigenetics & chromatin · 2026Review
- Review
- Blocking Lysine Crotonylation and Aerobic Glycolysis as Targeting Strategy Against mpox Virus Replication.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Epigenetic regulation of HIV-1 transcription: insights into latency mechanisms and therapeutic strategies.Frontiers in cellular and infection microbiology · 2026Review
- Microglial histone H3K18 crotonylation promotes STAT1 expression and induces cognitive deficit in Alzheimer disease.Frontiers in immunology · 2026Article
- HDAC1-mediated CDK1 decrotonylation inhibits colorectal cancer proliferation by regulating cell cycle and apoptosis.Frontiers in oncology · 2026Article
- The function and mechanism of protein acylation in the regulation of viral infection.Virulence · 2025Review
- Protein acylation in inflammatory diseases: from mechanisms to therapeutic strategies.Cell communication and signaling : CCS · 2025Review
- PKM2 crotonylation reprograms glycolysis in VSMCs, contributing to phenotypic switching.Oncogene · 2025Article
- A deep learning model for prediction of lysine crotonylation sites by fusing multi-features based on multi-head self-attention mechanism.Scientific reports · 2025Article
- RYBP promotes HIV-1 latency through promoting H2AK119ub and decreasing H3K4me3.Cell communication and signaling : CCS · 2025Article
- Histone crotonylation in tumors (Review).Molecular and clinical oncology · 2025Review
39 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Eradication of HIV-1 (HIV) is hindered by stable viral reservoirs. Viral latency is epigenetically regulated. While the effects of histone acetylation and methylation at the HIV long-terminal repeat (LTR) have been described, our knowledge of the proviral epigenetic landscape is incomplete. We report that a previously unrecognized epigenetic modification of the HIV LTR, histone crotonylation, is a regulator of HIV latency. Reactivation of latent HIV was achieved following the induction of histone crotonylation through increased expression of the crotonyl-CoA-producing enzyme acyl-CoA synthetase short-chain family member 2 (ACSS2). This reprogrammed the local chromatin at the HIV LTR through increased histone acetylation and reduced histone methylation. Pharmacologic inhibition or siRNA knockdown of ACSS2 diminished histone crotonylation-induced HIV replication and reactivation. ACSS2 induction was highly synergistic in combination with either a protein kinase C agonist (PEP005) or a histone deacetylase inhibitor (vorinostat) in reactivating latent HIV. In the SIV-infected nonhuman primate model of AIDS, the expression of ACSS2 was significantly induced in intestinal mucosa in vivo, which correlated with altered fatty acid metabolism. Our study links the HIV/SIV infection-induced fatty acid enzyme ACSS2 to HIV latency and identifies histone lysine crotonylation as a novel epigenetic regulator for HIV transcription that can be targeted for HIV eradication.
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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.