Cytosine methylation regulates oviposition in the pathogenic blood fluke Schistosoma mansoni

• Published in: Nature communications Vol. 2; no. 1; p. 424
• Main Authors: Geyer, Kathrin K., Rodríguez López, Carlos M., Chalmers, Iain W., Munshi, Sabrina E., Truscott, Martha, Heald, James, Wilkinson, Mike J., Hoffmann, Karl F.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.08.2011; Nature Publishing Group; Nature Pub. Group
• Subjects: 631/136; 631/208/200; 631/326/417/2549; 631/337/176/1988; Animals; Cytosine - metabolism; DNA Methylation; Female; Helminth Proteins - genetics; Helminth Proteins - metabolism; Humanities and Social Sciences; Humans; Mice; Mice, Inbred C57BL; multidisciplinary; Oviposition; Schistosoma mansoni - genetics; Schistosoma mansoni - pathogenicity; Schistosoma mansoni - physiology; Schistosomiasis mansoni - parasitology; Science; Science (multidisciplinary); Virulence
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms1433

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. The chronic disease schistosomiasis is caused by the blood fluke Schistosoma mansoni . By studying DNA modifications throughout the lifecycle of the pathogen, the authors identify DNA methylation as a factor in egg development and suggest that the epigenetic machinery responsible may be a therapeutic target.