Cytosine methylation regulates oviposition in the pathogenic blood fluke Schistosoma mansoni.
Cytosine methylation regulates oviposition in the pathogenic blood fluke Schistosoma mansoni.
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DOI：
10.1038/ncomms1433
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发表时间：
2011-08-09
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
与其他后生动物病原体相似，曼氏血吸虫在其复杂的生命周期和宿主相互作用中经历转录和发育调控。DNA甲基化作为控制这些过程的机制，迄今为止，在这种寄生虫中被低估了。在这里，我们展示了S. mansoni基因组。新型DNA甲基转移酶（SmDnmt 2）和甲基CpG结合域蛋白的转录共调节反映了胞嘧啶甲基化丰度的检测，并暗示存在功能性DNA甲基化机制。SmDnmt 2沉默后胞嘧啶甲基化的基因组损失和预测的叉头基因内高甲基化重复内含子的鉴定证实了这一论断。重要的是，由5-氮杂胞苷破坏卵生产和卵成熟建立了5-甲基胞嘧啶在这种寄生虫中的重要作用。这些发现提供了第一个功能确认这种表观遗传修饰在任何蠕虫物种和连接胞嘧啶甲基化机制扁形动物产卵过程。慢性血吸虫病是由曼氏血吸虫引起的。通过研究病原体整个生命周期中的DNA修饰，作者将DNA甲基化确定为卵子发育的一个因素，并认为负责的表观遗传机制可能是一个治疗靶点。
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.
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影响因子：
4.8
作者：
Fitzpatrick, Jennifer M.;Hirai, Yuriko;Hoffmann, Karl F.
通讯作者：
Hoffmann, Karl F.
影响因子：
56.9
作者：
Goll, MG;Kirpekar, F;Bestor, TH
通讯作者：
Bestor, TH
影响因子：
--
作者：
Katoh, M;Curk, T;Shaulsky, G
通讯作者：
Shaulsky, G
影响因子：
1.3
作者：
King, Charles H.;Dangerfield-Chay, Madeline
通讯作者：
Dangerfield-Chay, Madeline
DOI：
10.1016/0169-4758(95)80048-4
发表时间：
1995-08-01
期刊：
PARASITOLOGY TODAY
影响因子：
--
作者：
HIRAI, H;LOVERDE, PT
通讯作者：
LOVERDE, PT