Histone methylation changes are required for life cycle progression in the human parasite Schistosoma mansoni.

Autor: Roquis D; Technical University of Munich, Department of Plant Sciences, Freising, Germany., Taudt A; European Institute for the Biology of Aging, University of Groningen, University Medical Centre Groningen, AV Groningen, The Netherlands., Geyer KK; Institute of Biological, Environmental, and Rural Sciences (IBERS), Aberystwyth University, Penglais, Aberystwyth, Ceredigion, United Kingdom., Padalino G; Institute of Biological, Environmental, and Rural Sciences (IBERS), Aberystwyth University, Penglais, Aberystwyth, Ceredigion, United Kingdom., Hoffmann KF; Institute of Biological, Environmental, and Rural Sciences (IBERS), Aberystwyth University, Penglais, Aberystwyth, Ceredigion, United Kingdom., Holroyd N; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, United Kingdom., Berriman M; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, United Kingdom., Aliaga B; Univ. Perpignan Via Domitia, IHPE UMR 5244, CNRS, IFREMER, Univ. Montpellier, Perpignan, France., Chaparro C; Univ. Perpignan Via Domitia, IHPE UMR 5244, CNRS, IFREMER, Univ. Montpellier, Perpignan, France., Grunau C; Univ. Perpignan Via Domitia, IHPE UMR 5244, CNRS, IFREMER, Univ. Montpellier, Perpignan, France., Augusto RC; Univ. Perpignan Via Domitia, IHPE UMR 5244, CNRS, IFREMER, Univ. Montpellier, Perpignan, France.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2018 May 21; Vol. 14 (5), pp. e1007066. Date of Electronic Publication: 2018 May 21 (Print Publication: 2018).
DOI: 10.1371/journal.ppat.1007066
Abstrakt: Epigenetic mechanisms and chromatin structure play an important role in development. Their impact is therefore expected to be strong in parasites with complex life cycles and multiple, strikingly different, developmental stages, i.e. developmental plasticity. Some studies have already described how the chromatin structure, through histone modifications, varies from a developmental stage to another in a few unicellular parasites. While H3K4me3 profiles remain relatively constant, H3K27 trimethylation and bivalent methylation show strong variation. Inhibitors (A366 and GSK343) of H3K27 histone methyltransferase activity in S. mansoni efficiently blocked miracidium to sporocyst transition indicating that H3K27 trimethylation is required for life cycle progression. As S. mansoni is a multicellular parasite that significantly affects both the health and economy of endemic areas, a better understanding of fluke developmental processes within the definitive host will likely highlight novel disease control strategies. Towards this goal, we also studied H4K20me1 in female cercariae and adults. In particular, we found that bivalent trimethylation of H3K4 and H3K27 at the transcription start site of genes is a landmark of the cercarial stage. In cercariae, H3K27me3 presence and strong enrichment in H4K20me1 over long regions (10-100 kb) is associated with development related genes. Here, we provide a broad overview of the chromatin structure of a metazoan parasite throughout its most important lifecycle stages. The five developmental stages studied here present distinct chromatin structures, indicating that histone methylation plays an important role during development. Hence, components of the histone methylation (and demethylation) machinery may provide suitable Schistosomiasis control targets.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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