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Differential DNA methylation in discrete developmental stages of the parasitic nematode?Trichinella spiralis

机译:寄生线虫旋毛虫​​的离散发育阶段的差异DNA甲基化

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Background: DNA methylation plays an essential role in regulating gene expression under a variety of conditions and it has therefore been hypothesized to underlie the transitions between life cycle stages in parasitic nematodes. So far, however, 5'-cytosine methylation has not been detected during any developmental stage of the nematode Caenorhabditis elegans. Given the new availability of high-resolution methylation detection methods, an investigation of life cycle methylation in a parasitic nematode can now be carried out. Results: Here, using Methyl C-seq, we present the first study to confirm the existence of DNA methylation in the parasitic nematode Trichinella spiralis, and we characterize the methylomes of the three life-cycle stages of this food-borne infectious human pathogen. We observe a drastic increase in DNA methylation during the transition from the new born to mature stage, and we further identify parasitism-related genes that show changes in DNA methylation status between life cycle stages. Conclusions: Our data contribute to the understanding of the developmental changes that occur in an important human parasite, and raises the possibility that targeting DNA methylation processes may be a useful strategy in developing therapeutics to impede infection. In addition, our conclusion that DNA methylation is a mechanism for life cycle transition in T. spiralis prompts the question of whether this may also be the case in any other metazoans. Finally, our work constitutes the first report, to our knowledge, of DNA methylation in a nematode, prompting a re-evaluation of phyla in which this epigenetic mark was thought to be absent.
机译:背景:DNA甲基化在多种条件下均在调节基因表达中起着至关重要的作用,因此据推测,它是寄生线虫生命周期阶段之间过渡的基础。然而,到目前为止,在线虫秀丽隐杆线虫的任何发育阶段都未检测到5'-胞嘧啶甲基化。考虑到高分辨率甲基化检测方法的新可用性,现在可以对寄生线虫中的生命周期甲基化进行研究。结果:在这里,我们使用甲基C-seq进行了第一个研究,以确认在寄生线虫旋毛虫​​旋毛虫中存在DNA甲基化,并且我们表征了这种食源性传染性人类病原体三个生命周期阶段的甲基化。我们观察到从新生到成熟阶段的过渡过程中DNA甲基化的急剧增加,并且我们进一步鉴定了与寄生虫相关的基因,这些基因显示了生命周期各阶段DNA甲基化状态的变化。结论:我们的数据有助于理解重要人类寄生虫中发生的发育变化,并增加了靶向DNA甲基化过程可能成为开发治疗感染的有用策略的可能性。此外,我们的结论是DNA甲基化是螺旋藻生命周期过渡的一种机制,这提出了一个问题,即在任何其他后生动物中是否也可能存在这种情况。最后,据我们所知,我们的工作构成了线虫中DNA甲基化的第一份报告,这促使人们重新评估认为不存在这种表观遗传标记的门。

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