Cytosine methylation regulates oviposition in the pathogenic blood fluke Schistosoma mansoni

Kathrin K. Geyer, Carlos M. Rodríguez López, Iain W. Chalmers, Sabrina E. Munshi, Martha Truscott, James Heald, Mike J. Wilkinson, Karl F. Hoffmann

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

Abstract

Similar to other metazoan pathogens, Schistosoma mansoni undergoes transcriptional and developmental regulation during its complex lifecycle and host interactions. DNA methylation as a mechanism to control these processes has, to date, been discounted in this parasite. Here we show the first evidence for cytosine methylation in the S. mansoni genome. Transcriptional coregulation of novel DNA methyltransferase (SmDnmt2) and methyl-CpG-binding domain proteins mirrors the detection of cytosine methylation abundance and implicates the presence of a functional DNA methylation machinery. Genome losses in cytosine methylation upon SmDnmt2 silencing and the identification of a hypermethylated, repetitive intron within a predicted forkhead gene confirm this assertion. Importantly, disruption of egg production and egg maturation by 5-azacytidine establishes an essential role for 5-methylcytosine in this parasite. These findings provide the first functional confirmation for this epigenetic modification in any worm species and link the cytosine methylation machinery to platyhelminth oviposition processes.

Original languageEnglish
Article number424
JournalNature Communications
Volume2
Issue number1
DOIs
StatePublished - 2011

Bibliographical note

Funding Information:
This work was supported by research grants awarded to K.F.H. from the Wellcome Trust (WT084273), the Nuffield Foundation and the Sandler Center for Basic Research in Parasitic Diseases. We thank Dr Colin Jackson, Dr Emily Peak, Dr Samirah Perally and Ms Julie Hirst for assisting with schistosome lifecycle maintenance. We acknowledge Dr Fred Lewis for providing schistosome-infected Biomphalaria glabrata snails, Dr Dylan Phillips for support with laser confocal microscopy, Dr Candida Nibau for help with immunolocalization/GISH, Dr Scott Lawton for assistance in preparing cytological spreads, Dr Martin Swain for methylated locus dinucleotide context quantification and Dr Timothy Yoshino for supplying miracidia and sporocyst material. This work is dedicated to the scientific contributions and memory of our colleague and friend, Prof John Barrett, who passed away on 29 March 2011.

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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