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DNA methylation atlas and machinery in the developing and regenerating annelid Platynereis dumerilii
BMC Biology ( IF 4.4 ) Pub Date : 2021-08-03 , DOI: 10.1186/s12915-021-01074-5
Anabelle Planques 1 , Pierre Kerner 1 , Laure Ferry 2 , Christoph Grunau 3 , Eve Gazave 1 , Michel Vervoort 1
Affiliation  

Methylation of cytosines in DNA (5mC methylation) is a major epigenetic modification that modulates gene expression and constitutes the basis for mechanisms regulating multiple aspects of embryonic development and cell reprogramming in vertebrates. In mammals, 5mC methylation of promoter regions is linked to transcriptional repression. Transcription regulation by 5mC methylation notably involves the nucleosome remodeling and deacetylase complex (NuRD complex) which bridges DNA methylation and histone modifications. However, less is known about regulatory mechanisms involving 5mC methylation and their function in non-vertebrate animals. In this paper, we study 5mC methylation in the marine annelid worm Platynereis dumerilii, an emerging evolutionary and developmental biology model capable of regenerating the posterior part of its body post-amputation. Using in silico and experimental approaches, we show that P. dumerilii displays a high level of DNA methylation comparable to that of mammalian somatic cells. 5mC methylation in P. dumerilii is dynamic along the life cycle of the animal and markedly decreases at the transition between larval to post-larval stages. We identify a full repertoire of mainly single-copy genes encoding the machinery associated with 5mC methylation or members of the NuRD complex in P. dumerilii and show that this repertoire is close to the one inferred for the last common ancestor of bilaterians. These genes are dynamically expressed during P. dumerilii development and regeneration. Treatment with the DNA hypomethylating agent Decitabine impairs P. dumerilii larval development and regeneration and has long-term effects on post-regenerative growth. Our data reveal high levels of 5mC methylation in the annelid P. dumerilii, highlighting that this feature is not specific to vertebrates in the bilaterian clade. Analysis of DNA methylation levels and machinery gene expression during development and regeneration, as well as the use of a chemical inhibitor of DNA methylation, suggest an involvement of 5mC methylation in P. dumerilii development and regeneration. We also present data indicating that P. dumerilii constitutes a promising model to study biological roles and mechanisms of DNA methylation in non-vertebrate bilaterians and to provide new knowledge about evolution of the functions of this key epigenetic modification in bilaterian animals.

中文翻译:

圆环动物发育和再生过程中的 DNA 甲基化图谱和机制

DNA 中胞嘧啶的甲基化(5mC 甲基化)是一种主要的表观遗传修饰,可调节基因表达,并构成调节脊椎动物胚胎发育和细胞重编程多个方面的机制的基础。在哺乳动物中,启动子区域的 5mC 甲基化与转录抑制有关。5mC 甲基化的转录调控特别涉及核小体重塑和脱乙酰酶复合物(NuRD 复合物),该复合物桥接 DNA 甲基化和组蛋白修饰。然而,人们对涉及 5mC 甲基化的调控机制及其在非脊椎动物中的功能知之甚少。在本文中,我们研究了海洋环节动物 Platynereis dumerilii 中的 5mC 甲基化,这是一种新兴的进化和发育生物学模型,能够在截肢后再生其身体后部。使用计算机和实验方法,我们发现杜美氏松树表现出与哺乳动物体细胞相当的高水平 DNA 甲基化。P. dumerilii 中的 5mC 甲基化在动物的生命周期中是动态的,并且在幼虫到幼虫后阶段的过渡期间显着降低。我们鉴定了杜美氏 P. dumerilii 中编码与 5mC 甲基化或 NuRD 复合体成员相关的机制的主要单拷贝基因的完整库,并表明该库与推断的两侧对称动物最后共同祖先的库接近。这些基因在杜氏拟青霉发育和再生过程中动态表达。DNA 低甲基化剂地西他滨处理会损害杜美幼虫的发育和再生,并对再生后的生长产生长期影响。我们的数据揭示了环节动物 P. dumerilii 中高水平的 5mC 甲基化,强调这一特征并非两侧对称进化枝中的脊椎动物所特有。对发育和再生过程中 DNA 甲基化水平和机械基因表达的分析,以及 DNA 甲基化化学抑制剂的使用,表明 5mC 甲基化参与杜梅氏 P. dumerilii 发育和再生。我们还提供的数据表明,P. dumerilii 构成了一个有前途的模型,用于研究非脊椎动物两侧对称动物中 DNA 甲基化的生物学作用和机制,并提供有关两侧对称动物中这一关键表观遗传修饰功能进化的新知识。
更新日期:2021-08-03
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