title: Cytosine methylation regulates oviposition in the pathogenic blood fluke Schistosoma mansoni.
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.
authors.affiliation: Institute of Biological, Environmental and Rural Sciences (IBERS), Aberystwyth University, Penglais Campus, Aberystwyth SY23 3DA, UK.
authors.forename: Kathrin K
authors.initials: KK
authors.lastname: Geyer
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Rodríguez López
authors.forename: Iain W
authors.initials: IW
authors.lastname: Chalmers
authors.forename: Sabrina E
authors.initials: SE
authors.lastname: Munshi
authors.forename: Martha
authors.initials: M
authors.lastname: Truscott
authors.forename: James
authors.initials: J
authors.lastname: Heald
authors.forename: Mike J
authors.initials: MJ
authors.lastname: Wilkinson
authors.forename: Karl F
authors.initials: KF
authors.lastname: Hoffmann
mesh_terms: D000818:Animals; D003596:Cytosine / Q000378:metabolism*; D019175:DNA Methylation; D005260:Female; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010058:Oviposition; D012550:Schistosoma mansoni / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D012555:Schistosomiasis mansoni / Q000469:parasitology*; D014774:Virulence
chemical_list: D015801:Helminth Proteins; D003596:Cytosine