Institute of Biological, Environmental and Rural Sciences (IBERS), Aberystwyth University, Penglais Campus, Aberystwyth SY23 3DA, UK.
Nat Commun. 2011 Aug 9;2:424. 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.
类似于其他后生动物病原体，曼氏血吸虫在其复杂的生命周期和宿主相互作用过程中经历转录和发育调控。迄今为止，这种寄生虫的 DNA 甲基化作为一种控制这些过程的机制已被排除。在这里，我们首次展示了曼氏血吸虫基因组中胞嘧啶甲基化的证据。新型 DNA 甲基转移酶 (SmDnmt2) 和甲基-CpG 结合域蛋白的转录核心调控反映了胞嘧啶甲基化丰度的检测，并暗示存在功能齐全的 DNA 甲基化机制。SmDnmt2 沉默后胞嘧啶甲基化的基因组丢失，以及在预测的叉头基因内发现一个高甲基化的重复内含子，证实了这一说法。重要的是，5-氮杂胞苷对产卵和卵成熟的破坏确立了 5-甲基胞嘧啶在这种寄生虫中的重要作用。这些发现首次在任何线虫物种中为这种表观遗传修饰提供了功能确认，并将胞嘧啶甲基化机制与扁形动物产卵过程联系起来。
