Cytosine methylation is a conserved epigenetic feature found throughout the phylum Platyhelminthes

Abstract

BackgroundThe phylum Platyhelminthes (flatworms) contains an important group of bilaterian organisms responsible for many debilitating and chronic infectious diseases of human and animal populations inhabiting the planet today. In addition to their biomedical and veterinary relevance, some platyhelminths are also frequently used models for understanding tissue regeneration and stem cell biology. Therefore, the molecular (genetic and epigenetic) characteristics that underlie trophic specialism, pathogenicity or developmental maturation are likely to be pivotal in our continued studies of this important metazoan group. Indeed, in contrast to earlier studies that failed to detect evidence of cytosine or adenine methylation in parasitic flatworm taxa, our laboratory has recently defined a critical role for cytosine methylation in Schistosoma mansoni oviposition, egg maturation and ovarian development. Thus, in order to identify whether this epigenetic modification features in other platyhelminth species or is a novelty of S. mansoni, we conducted a study simultaneously surveying for DNA methylation machinery components and DNA methylation marks throughout the phylum using both parasitic and non-parasitic representatives.ResultsFirstly, using both S. mansoni DNA methyltransferase 2 (SmDNMT2) and methyl-CpG binding domain protein (SmMBD) as query sequences, we illustrate that essential DNA methylation machinery components are well conserved throughout the phylum. Secondly, using both molecular (methylation specific amplification polymorphism, MSAP) and immunological (enzyme-linked immunoabsorbent assay, ELISA) methodologies, we demonstrate that representative species (Echinococcus multilocularis, Protopolystoma xenopodis, Schistosoma haematobium, Schistosoma japonicum, Fasciola hepatica and Polycelis nigra) within all four platyhelminth classes (Cestoda, Monogenea, Trematoda and ‘Turbellaria’) contain methylated cytosines within their genome compartments.ConclusionsCollectively, these findings provide the first direct evidence for a functionally conserved and enzymatically active DNA methylation system throughout the Platyhelminthes. Defining how this epigenetic feature shapes phenotypic diversity and development within the phylum represents an exciting new area of metazoan biology.

Regulation of DNA methylation on key parasitism genes of Cysticercus cellulosae revealed by integrative epigenomic-transcriptomic analyses

“…T. solium cysticerci have developed diverse mechanisms to protect themselves from host immune attack [26], among which epigenetics may play an important role in gene regulation related to parasitism [24]. Recently, Geyer et al found that essential DNA methylation machinery components, such as DNMT2 and MBD, are well conserved throughout the Platyhelminthes [4, 27]. Invertebrate DNMT2s are believed to retain strong DNA methyltransferase activity [28], which is different from vertebrate DNMT2s, which are considered tRNA methyltransferases [29].…”

Egg-specific expression of protein with DNA methyltransferase activity in the biocarcinogenic liver fluke Clonorchis sinensis

“…However, DNMT2-only or DNMT-free organisms contradicted the widely accepted role of DNA methylation in eukaryotes (Jeltsch, 2010;Raddatz et al 2013). 1; Geyer et al 2013). 1; Geyer et al 2013).…”

Epigenetics in Schistosomes: What We Know and What We Need Know

“…Recently, cytosine methylation was found to be a conserved epigenetic feature throughout the phylum Platyhelminthes, including Schistosoma haematobium, Schistosoma japonicum , and S. mansoni (Geyer et al, 2013). In addition to cytosine methylation, the arginine methyltransferase PRMT1 homolog was identified in S. mansoni and S. japonicum (Mansure et al, 2005; Diao et al, 2014).…”