来自Cell的科研成果

来自美、中、日、西等多国的研究人员证明了启动子相关CGIs的DNA甲基化可以从小白鼠父母传给小白鼠的后代，这些观察结果对于证明哺乳动物中的代际表观遗传提供了具体的步骤。

Summary

Transgenerational epigenetic inheritance in mammals remains a debated subject. Here, we demonstrate that DNA methylation of promoter-associated CpG islands (CGIs) can be transmitted from parents to their offspring in mice. We generated DNA methylation-edited mouse embryonic stem cells (ESCs), in which CGIs of two metabolism-related genes, the Ankyrin repeat domain 26 and the low-density lipoprotein receptor, were specifically methylated and silenced. DNA methylation-edited mice generated by microinjection of the methylated ESCs exhibited abnormal metabolic phenotypes. Acquired methylation of the targeted CGI and the phenotypic traits were maintained and transmitted across multiple generations. The heritable CGI methylation was subjected to reprogramming in parental PGCs and subsequently reestablished in the next generation at post-implantation stages. These observations provide a concrete step toward demonstrating transgenerational epigenetic inheritance in mammals, which may have implications in our understanding of evolutionary biology as well as the etiology, diagnosis, and prevention of non-genetically inherited human diseases.

研究结论：

哺乳动物中的代际表观遗传仍然是一个有争议的课题。在这里，我们证明了在小鼠中，启动子相关的CpG岛（CGIs）的DNA甲基化可以从父母传递给子代。我们生成了经过DNA甲基化编辑的小鼠胚胎干细胞（ESCs），其中两个与代谢相关的基因，Ankyrin重复结构域26和低密度脂蛋白受体的CGIs被特异性甲基化并沉默。通过将甲基化的ESCs进行微注射产生的甲基化小鼠展现了异常的代谢表型。目标CGI的获得性甲基化和表型特征在多个世代中得以保持和传递。可遗传的CGI甲基化在父母PGCs中经历了重编程，并在下一代在植入后阶段重新建立。这些观察结果对于证明哺乳动物中的代际表观遗传提供了一个具体的步骤，这可能对我们理解进化生物学以及非遗传性人类疾病的病因学、诊断和预防有重要意义。

Yuta Takahashi . Mariana Morales Valencia . Yang Yu  Yasuo Ouchi . Kazuki Takahashi .Maxim Nikolaievich Shokhirev  Kathryn Lande · April E. Wiiams   Chiara Fresia · Masakazu Kurita 。Tomoaki Hishida . Kensaku Shojima . Fumiyuki Hatanaka . Estrella Nunez-Delicado .Concepcion Rodriguez Esteban . Juan Carlos lzpisua Belmonte

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