ArticlePLoS pathogens2014
Epigenetic changes modulate schistosome egg formation and are a novel target for reducing transmission of schistosomiasis.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 64 citations in OpenAlex.
- Schistosoma japonicum histone acetyltransferase 1 (SjHAT1): A novel anti-schistosomal drug target.PLoS pathogens · 2026Article
- The retinoic acid family-like nuclear receptor SmRAR identified by single-cell transcriptomics of ovarian cells controls oocyte differentiation in Schistosoma mansoni.Nucleic acids research · 2025Article
- Quantum-Mechanically Refined, Dynamics-Coupled, and AI-Augmented Elucidation of Epigenetic Inhibition: An In Silico Paradigm Targeting HDAC8 ofJournal of tropical medicine · 2025Article
- Schistosomicidal effects of histone acetyltransferase inhibitors against Schistosoma japonicum juveniles and adult worms in vitro.PLoS neglected tropical diseases · 2024Article
- Small Molecule Ligands of the BET-like Bromodomain,Journal of medicinal chemistry · 2023Article
- Article
- Chemical modulation ofWellcome open research · 2023Article
- JQ-1 ameliorates schistosomiasis liver granuloma in mice by suppressing male and female reproductive systems and egg development of Schistosoma japonicum.PLoS neglected tropical diseases · 2022Article
- Effects of Environmental Conditions on Nephron Number: Modeling Maternal Disease and Epigenetic Regulation in Renal Development.International journal of molecular sciences · 2021Article
- Epigenetic Markers Associated with Schistosomiasis.Helminthologia · 2021Article
- Long non-coding RNA levels can be modulated by 5-azacytidine in Schistosoma mansoni.Scientific reports · 2020Article
- Pharmacological inhibition of lysine-specific demethylase 1 (LSD1) induces global transcriptional deregulation and ultrastructural alterations that impair viability in Schistosoma mansoni.PLoS neglected tropical diseases · 2020Article
- Inhibition of 19S proteasome deubiquitinating activity in Schistosoma mansoni affects viability, oviposition, and structural changes.Parasitology research · 2020Article
- The antischistosomal potential of GSK-J4, an H3K27 demethylase inhibitor: insights from molecular modeling, transcriptomics and in vitro assays.Parasites & vectors · 2020Article
- Epigenetic and parasitological parameters are modulated in EBi3-/- mice infected with Schistosoma mansoni.PLoS neglected tropical diseases · 2020Article
- The repositioning of epigenetic probes/inhibitors identifies new anti-schistosomal lead compounds and chemotherapeutic targets.PLoS neglected tropical diseases · 2019Article
- In vitro and in vivo activities of DW-3-15, a commercial praziquantel derivative, against Schistosoma japonicum.Parasites & vectors · 2019Article
- Effects of the Environment on Developmental Plasticity and Infection Success ofFrontiers in microbiology · 2019Review
- Combining bioinformatics, cheminformatics, functional genomics and whole organism approaches for identifying epigenetic drug targets in Schistosoma mansoni.International journal for parasitology. Drugs and drug resistance · 2018Article
- Inhibition of histone methyltransferase EZH2 in Schistosoma mansoni in vitro by GSK343 reduces egg laying and decreases the expression of genes implicated in DNA replication and noncoding RNA metabolism.PLoS neglected tropical diseases · 2018Article
Corrections and comments
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Authors and funding
10 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Treatment and control of schistosomiasis relies on the only available drug, praziquantel, and the search for alternative chemotherapeutic agents is therefore urgent. Egg production is required for the transmission and immunopathology of schistosomiasis and females of S. mansoni lay 300 eggs daily. A large fraction of the total mRNA in the mature female worm encodes one eggshell protein, Smp14. We report that the nuclear receptors SmRXR1 and SmNR1 regulate Smp14 transcription through the recruitment of two histone acetyltransferases (HATs), SmGCN5 and SmCBP1. The treatment of HEK293 cells with histone deacetylase (HDAC) inhibitors (NaB or TSA) produced an 8-fold activation of the SmRXR1/SmNR1-mediated Smp14 promoter activity. Incubation with synthetic HAT inhibitors, including PU139, significantly impaired the Smp14 promoter activity in these cells. Worm pairs cultivated in the presence of PU139 exhibited limited expression of Smp14 mRNA and protein. ChIP analysis demonstrated chromatin condensation at the Smp14 promoter site in worms treated with PU139. ChIP also revealed the presence of H3K27me3 and the absence of RNA Pol II at the Smp14 promoter region in the PU139-treated worms. Most significantly, the PU139-mediated inhibition of Smp14 expression resulted in a significant number of abnormal eggs as well as defective eggs within the ootype. In addition, scanning electron microscopy revealed structural defects and unformed eggshells, and vitelline cell leakage was apparent. The dsRNAi-targeting of SmGCN5 or SmCBP1 significantly decreased Smp14 transcription and protein synthesis, which compromised the reproductive system of mature female worms, egg-laying and egg morphology. Our data strongly suggest that the inhibition of Smp14 expression targeting SmGCN5 and/or SmCBP1 represents a novel and effective strategy to control S. mansoni egg development.
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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.