ArticleMolecular microbiology2010
Histone deacetylases play distinct roles in telomeric VSG expression site silencing in African trypanosomes.
Article in Molecular microbiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 81 citations in OpenAlex.
- Article
- A factor integrating transcription and repression of surface antigen genes in African trypanosomes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Histone post-translational modifications of Leishmania braziliensis.Scientific data · 2025Article
- Parasite nucleosomes: Chromatin dynamics rewired.PLoS pathogens · 2025Article
- Targeting histone acetylation to overcome drug resistance in the parasitebioRxiv : the preprint server for biology · 2025Article
- TelAP2 links TelAP1 to the telomere complex in Trypanosoma brucei.Scientific reports · 2024Article
- Chemical Inhibition of Bromodomain Proteins in Insect-Stage African Trypanosomes Perturbs Silencing of the Variant Surface Glycoprotein Repertoire and Results in Widespread Changes in the Transcriptome.Microbiology spectrum · 2023Article
- Advances in Protozoan Epigenetic Targets and Their Inhibitors for the Development of New Potential Drugs.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Stage-specific transcription activator ESB1 regulates monoallelic antigen expression in Trypanosoma brucei.Nature microbiology · 2022Article
- Metacyclogenesis defects and gene expression hallmarks of histone deacetylase 4-deficient Trypanosoma cruzi cells.Scientific reports · 2021Article
- A systematic analysis ofGenome research · 2021Article
- A nuclear enterprise: zooming in on nuclear organization and gene expression control in the African trypanosome.Parasitology · 2021Review
- An updated map of Trypanosoma cruzi histone post-translational modifications.Scientific data · 2021Article
- May the Odds Be Ever in Your Favor: Non-deterministic Mechanisms Diversifying Cell Surface Molecule Expression.Frontiers in cell and developmental biology · 2021Review
- Protein Lactylation Critically Regulates Energy Metabolism in the Protozoan ParasiteFrontiers in cell and developmental biology · 2021Article
- Review
- Article
- Histone deacetylases as targets for antitrypanosomal drugs.Future science OA · 2018Review
- Transcriptional Regulation of Telomeric Expression Sites and Antigenic Variation in Trypanosomes.Current genomics · 2018Review
- Epigenetic Regulation of Transcription in Trypanosomatid Protozoa.Current genomics · 2018Review
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
Abstract
African trypanosomes evade the host immune response through antigenic variation, which is achieved by periodically expressing different variant surface glycoproteins (VSGs). VSG expression is monoallelic such that only one of approximately 15 telomeric VSG expression sites (ESs) is transcribed at a time. Epigenetic regulation is involved in VSG control but our understanding of the mechanisms involved remains incomplete. Histone deacetylases are potential drug targets for diseases caused by protozoan parasites. Here, using recombinant expression we show that the essential Trypanosoma brucei deacetylases, DAC1 (class I) and DAC3 (class II) display histone deacetylase activity. Both DAC1 and DAC3 are nuclear proteins in the bloodstream stage parasite, while only DAC3 remains concentrated in the nucleus in insect-stage cells. Consistent with developmentally regulated localization, DAC1 antagonizes SIR2rp1-dependent telomeric silencing only in the bloodstream form, indicating a conserved role in the control of silent chromatin domains. In contrast, DAC3 is specifically required for silencing at VSG ES promoters in both bloodstream and insect-stage cells. We conclude that DAC1 and DAC3 play distinct roles in subtelomeric gene silencing and that DAC3 represents the first readily druggable target linked to VSG ES control in the African trypanosome.
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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.