ArticlePLoS pathogens2010
Histone deacetylases play a major role in the transcriptional regulation of the Plasmodium falciparum life cycle.
Article in PLoS pathogens, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 146 citations in OpenAlex.
- Hydroxamic Acids as HDAC Inhibitor Drug Leads for Malaria.Medicinal research reviews · 2026Review
- From Epigenetic Regulation to Protein Degradation: Emerging Strategies for Anti-Infective Drug Discovery.International journal of molecular sciences · 2026Review
- Human genetic variations conferring resistance to malaria.Journal of translational medicine · 2025Review
- Targeting histone acetylation to overcome drug resistance in the parasitebioRxiv : the preprint server for biology · 2025Article
- Epigenetic regulation as a therapeutic target in the malaria parasite Plasmodium falciparum.Malaria journal · 2024Review
- 1,3-Diphenylureido hydroxamate as a promising scaffold for generation of potent antimalarial histone deacetylase inhibitors.Scientific reports · 2023Article
- Epidrugs as Promising Tools to EliminatePharmaceutics · 2023Article
- Epigenetic Regulation and Chromatin Remodeling in Malaria Parasites.Annual review of microbiology · 2023Review
- TgKDAC4: A Unique Deacetylase ofMicroorganisms · 2023Article
- Promising antimalarial hits from phenotypic screens: a review of recently-described multi-stage actives and their modes of action.Frontiers in cellular and infection microbiology · 2023Review
- Harnessing the cyclization strategy for new drug discovery.Acta pharmaceutica Sinica. B · 2022Review
- New Transmission-Selective Antimalarial Agents through Hit-to-Lead Optimization of 2-([1,1'-Biphenyl]-4-carboxamido)benzoic Acid Derivatives.Chembiochem : a European journal of chemical biology · 2022Article
- Review
- Theileria annulata histone deacetylase 1 (TaHDAC1) initiates schizont to merozoite stage conversion.Scientific reports · 2022Article
- Histone Modification Landscapes as a Roadmap for Malaria Parasite Development.Frontiers in cell and developmental biology · 2022Review
- Impact of Sickle Cell Trait Hemoglobin on the Intraerythrocytic Transcriptional Program of Plasmodium falciparum.mSphere · 2021Article
- Cyclic Tetrapeptide HDAC Inhibitors with ImprovedACS infectious diseases · 2021Article
- A unique GCN5 histone acetyltransferase complex controls erythrocyte invasion and virulence in the malaria parasite Plasmodium falciparum.PLoS pathogens · 2021Article
- Antitheilerial Activity of the Anticancer Histone Deacetylase Inhibitors.Frontiers in microbiology · 2021Article
- Dynamic Chromatin Structure and Epigenetics Control the Fate of Malaria Parasites.Trends in genetics : TIG · 2021Review
19 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The apparent paucity of molecular factors of transcriptional control in the genomes of Plasmodium parasites raises many questions about the mechanisms of life cycle regulation in these malaria parasites. Epigenetic regulation has been suggested to play a major role in the stage specific gene expression during the Plasmodium life cycle. To address some of these questions, we analyzed global transcriptional responses of Plasmodium falciparum to a potent inhibitor of histone deacetylase activities (HDAC). The inhibitor apicidin induced profound transcriptional changes in multiple stages of the P. falciparum intraerythrocytic developmental cycle (IDC) that were characterized by rapid activation and repression of a large percentage of the genome. A major component of this response was induction of genes that are otherwise suppressed during that particular stage of the IDC or specific for the exo-erythrocytic stages. In the schizont stage, apicidin induced hyperacetylation of histone lysine residues H3K9, H4K8 and the tetra-acetyl H4 (H4Ac4) and demethylation of H3K4me3. Interestingly, we observed overlapping patterns of chromosomal distributions between H4K8Ac and H3K4me3 and between H3K9Ac and H4Ac4. There was a significant but partial association between the apicidin-induced gene expression and histone modifications, which included a number of stage specific transcription factors. Taken together, inhibition of HDAC activities leads to dramatic de-regulation of the IDC transcriptional cascade, which is a result of both disruption of histone modifications and up-regulation of stage specific transcription factors. These findings suggest an important role of histone modification and chromatin remodeling in transcriptional regulation of the Plasmodium life cycle. This also emphasizes the potential of P. falciparum HDACs as drug targets for malaria chemotherapy.
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