小柯机器人

中国科学院动物研究所Fan Guo和Hongmei Wang共同合作，近期取得重要工作进展。他们对小鼠胚胎和生殖系发育过程中DNA羟甲基化和甲基化的动态过程进行了研究。相关研究成果2022年12月20在线发表于《自然—遗传学》杂志上。

据介绍，在哺乳动物中，DNA 5-羟甲基胞嘧啶（5hmC）在胚胎早期发育过程中参与甲基化重编程。然而，5hmC在多大程度上参与了全基因组甲基化重编程，目前还不清楚。

研究人员用亲代等位基因特异性描绘了小鼠早期胚胎和生殖细胞中的5hmC图谱。与受精卵中的从头甲基化或维持甲基化相比，DNA羟甲基化与DNA去甲基化最密切相关，而5hmC靶向于受精后外胚层中特定的重新甲基化位点。5hmC的产生也需要DNA复制，尤其是在雌性原核中。由于母体缺乏Nlrp14，小鼠受精卵中Dnmt1/Uhrf1的核定位异常，导致DNA复制偶联的被动去甲基化缺陷和5hmC沉积受损，揭示了全基因组5-甲基胞嘧啶（5mC）维持和Tet介导的氧化之间的差异。

总之，这一工作为研究早期胚胎发育中的表观遗传学调控提供了深刻的见解和宝贵的资源。

附：英文原文

Title: Dynamics of DNA hydroxymethylation and methylation during mouse embryonic and germline development

Author: Yan, Rui, Cheng, Xin, Gu, Chan, Xu, Yanhong, Long, Xin, Zhai, Jinglei, Sun, Fengyuan, Qian, Jingjing, Du, Yarui, Wang, Hongmei, Guo, Fan

Issue&Volume: 2022-12-20

Abstract: In mammals, DNA 5-hydroxymethylcytosine (5hmC) is involved in methylation reprogramming during early embryonic development. Yet, to what extent 5hmC participates in genome-wide methylation reprogramming remains largely unknown. Here, we characterize the 5hmC landscapes in mouse early embryos and germ cells with parental allele specificity. DNA hydroxymethylation was most strongly correlated with DNA demethylation as compared with de novo or maintenance methylation in zygotes, while 5hmC was targeted to particular de novo methylated sites in postimplantation epiblasts. Surprisingly, DNA replication was also required for 5hmC generation, especially in the female pronucleus. More strikingly, aberrant nuclear localization of Dnmt1/Uhrf1 in mouse zygotes due to maternal deficiency of Nlrp14 led to defects in DNA-replication-coupled passive demethylation and impaired 5hmC deposition, revealing the divergency between genome-wide 5-methylcytosine (5mC) maintenance and Tet-mediated oxidation. In summary, our work provides insights and a valuable resource for the study of epigenetic regulation in early embryo development.

DOI: 10.1038/s41588-022-01258-x

Source: https://www.nature.com/articles/s41588-022-01258-x

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
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投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex