The Epigenome of Schistosoma mansoni Provides Insight about How Cercariae Poise Transcription until Infection

Type Article
Date 2015-08
Language English
Author(s) Roquis DavidORCID1, 2, Lepesant Julie M. J.1, 2, Picard Marion A. L.1, 2, Freitag Michael3, Parrinello Hugues4, Groth MarcoORCID5, Emans Remi2, Cosseau Celine1, 2, Grunau ChristophORCID1, 2
Affiliation(s) 1 : Univ Perpignan, F-66025 Perpignan, France.
2 : CNRS, UMR 5244, IHPE, Perpignan, France.
3 : Oregon State Univ, Corvallis, OR 97331 USA.
4 : CNRS, GenomiX IBiSA, Montpellier, France.
5 : Fritz Lipmann Inst, Leibniz Inst Age Research, Jena, Germany.
Source Plos Neglected Tropical Diseases (1935-2735) (Public Library Science), 2015-08 , Vol. 9 , N. 8 , P. e0003853 (22p.)
DOI 10.1371/journal.pntd.0003853
WOS© Times Cited 34
Abstract

Background Chromatin structure can control gene expression and can define specific transcription states. For example, bivalent methylation of histone H3K4 and H3K27 is linked to poised transcription in vertebrate embryonic stem cells (ESC). It allows them to rapidly engage specific developmental pathways. We reasoned that non-vertebrate metazoans that encounter a similar developmental constraint (i.e. to quickly start development into a new phenotype) might use a similar system. Schistosomes are parasitic platyhelminthes that are characterized by passage through two hosts: a mollusk as intermediate host and humans or rodents as definitive host. During its development, the parasite undergoes drastic changes, most notable immediately after infection of the definitive host, i.e. during the transition from the free-swimming cercariae into adult worms. Methodology/Principal Findings We used Chromatin Immunoprecipitation followed by massive parallel sequencing (ChIP-Seq) to analyze genome-wide chromatin structure of S. mansoni on the level of histone modifications (H3K4me3, H3K27me3, H3K9me3, and H3K9ac) in cercariae, schistosomula and adults (available at http://genome.univ-perp.fr). We saw striking differences in chromatin structure between the developmental stages, but most importantly we found that cercariae possess a specific combination of marks at the transcription start sites (TSS) that has similarities to a structure found in ESC. We demonstrate that in cercariae no transcription occurs, and we provide evidences that cercariae do not possess large numbers of canonical stem cells. Conclusions/Significance We describe here a broad view on the epigenome of a metazoan parasite. Most notably, we find bivalent histone H3 methylation in cercariae. Methylation of H3K27 is removed during transformation into schistosomula (and stays absent in adults) and transcription is activated. In addition, shifts of H3K9 methylation and acetylation occur towards upstream and downstream of the transcriptional start site (TSS). We conclude that specific H3 modifications are a phylogenetically older and probably more general mechanism, i.e. not restricted to stem cells, to poise transcription. Since adult couples must form to cause the disease symptoms, changes in histone modifications appear to be crucial for pathogenesis and represent therefore a therapeutic target.

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S1 Table. (a) Primers targeting regions with bivalent H3K4me3 and H3K27me3 marks in cercariae, and monovalent H3K4me3 marks in adults. (b) Primers targeting regions with H3K4me3 differences between... 1 14 KB Open access
S2 Table. H3K4me3 peaks in putative polycistrons with a maximum intergenic distance of 200bp. 48 KB Open access
S3 Table. DESeq results for ChIP-Seq on repetitive sequences. 1 MB Open access
S4 Table. List of transcripts for which TSS has H3K4me3 and H3K27me in cercariae, evidence from GeneDB (for Smp_######) and from AmiGO v.1.8 (for TCONS_########). 1 54 KB Open access
S1 Fig. Relative enrichment compared to the alpha-tubulin locus: ChIP-Seq vs qPCR, p-value is given for the t-test of the null hypothesis that the corresponding slope is equal to zero against... 99 KB Open access
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How to cite 

Roquis David, Lepesant Julie M. J., Picard Marion A. L., Freitag Michael, Parrinello Hugues, Groth Marco, Emans Remi, Cosseau Celine, Grunau Christoph (2015). The Epigenome of Schistosoma mansoni Provides Insight about How Cercariae Poise Transcription until Infection. Plos Neglected Tropical Diseases, 9(8), e0003853 (22p.). Publisher's official version : https://doi.org/10.1371/journal.pntd.0003853 , Open Access version : https://archimer.ifremer.fr/doc/00615/72712/