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

http://ir.library.oregonstate.edu/concern/articles/5d86p1939

Supporting Information available online at:  http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0003853#sec020

This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Public Library of Science. The published article can be found at:  http://journals.plos.org/plosntds/

Data Availability Statement: ChIP-Seq and RNASeq fastq files are available at the NCBI SRA as studies SRP034587 and SRP035609, respectively. We also a provide a Gbrowse interface at http:// genome.univ-perp.fr

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  • 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. Author Summary: The blood fluke Schistosoma mansoni causes intestinal bilharzia. The parasite has a complex life cycle in which a freshwater snail serves as intermediate host from which the human infecting larvae hatch. These larvae will actively seek skin contact, penetrate through the epithelium and start developing straight away into adult worms. Development from larvae into adults needs thorough adjustment of gene expression through repositioning or modification of proteins that are associated with DNA (the chromatin). We decided to compare the chromatin of human infective larvae (cercariae), the first developmental stage after infection of the vertebrate host (schistosomula) and adults of S. mansoni. We found that cercariae possess chromatin structures (modifications of histone H3) around the beginning of genes that are very different from schistosomula and adults. We conclude that this structure serves to keep gene transcription in a poised state, i.e. transcription is initiated and can start immediately when the blocking histone modification is removed. A similar type of histone modification was found in embryonic stem cells of vertebrates and our data indicate that it is either a more ancient and/or more general means to poise transcription than previously assumed. Since many parasites possess infective stages that develop rapidly within the host, this particular chromatin structure could be a therapeutic target for a new class of antiparasitic drugs.
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  • Roquis, D., Lepesant, J. M., Picard, M. A., Freitag, M., Parrinello, H., Groth, M., ... & Grunau, C. (2015). The Epigenome of Schistosoma mansoni Provides Insight about How Cercariae Poise Transcription until Infection. PLoS Neglected Tropical Diseases, 9(8), e0003853. doi:10.1371/journal.pntd.0003853
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  • description.provenance : Submitted by Patricia Black (patricia.black@oregonstate.edu) on 2015-10-07T15:10:43Z No. of bitstreams: 2 license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5) FreitagMichaelBiochemEpigenomeSchistosomaMansoni.pdf: 4985184 bytes, checksum: 60c6a5ae1661a46730c59208e3812aac (MD5)
  • description.provenance : Approved for entry into archive by Patricia Black(patricia.black@oregonstate.edu) on 2015-10-07T15:11:57Z (GMT) No. of bitstreams: 2 license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5) FreitagMichaelBiochemEpigenomeSchistosomaMansoni.pdf: 4985184 bytes, checksum: 60c6a5ae1661a46730c59208e3812aac (MD5)
  • description.provenance : Made available in DSpace on 2015-10-07T15:11:57Z (GMT). No. of bitstreams: 2 license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5) FreitagMichaelBiochemEpigenomeSchistosomaMansoni.pdf: 4985184 bytes, checksum: 60c6a5ae1661a46730c59208e3812aac (MD5) Previous issue date: 2015-08

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