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

Abstract:

: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.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Roquis D,Taudt A,Geyer KK,Padalino G,Hoffmann KF,Holroyd N,Berriman M,Aliaga B,Chaparro C,Grunau C,Augusto RC

doi

10.1371/journal.ppat.1007066

subject

Has Abstract

pub_date

2018-05-21 00:00:00

pages

e1007066

issue

5

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-18-00235

journal_volume

14

pub_type

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