天津大学元英进研究团队取得一项新突破。他们报道了在小鼠早期胚胎中重新组装和传递合成的超大规模人类DNA。相关论文于2025年7月10日发表于国际顶尖学术期刊《自然—方法学》杂志上。

在这项研究中，研究人员开发了SynNICE，一种将完整的、原始的、合成的兆基（Mb）级人类DNA组装并传递到早期无母胚胎中的方法，以研究从头表观遗传调控。通过组装和传递一个1.14Mb的人AZFa （hAZFa）位点，研究小组观察到小鼠组蛋白在单细胞阶段的自发结合和DNA甲基化的建立。值得注意的是，DNA从头甲基化在没有H3K9me3强化的重复序列上强烈富集。

此外，在它们的细胞阶段启动的hAZFa转录受到新建立的DNA甲基化的调节。这种方法为探索高等动物从头开始的表观基因组调控机制提供了一个独特的平台。

据介绍，天然染色体上的表观遗传修饰被遗传并维持在默认状态，这使得去除内在标记以研究其建立的基本原理及其对转录调控的进一步影响具有挑战性。

附：英文原文

Title: De novo assembly and delivery of synthetic megabase-scale human DNA into mouse early embryos

Author: Liu, Yue, Zhou, Jianting, Liu, Duo, Hu, Xiaoyu, Yang, Lin, Song, Xue-Ru, Jin, Xiao-Dong, Xie, Wei, Yang, Luhan, Liu, Zichuan, Yuan, Ying-Jin

Issue&Volume: 2025-07-10

Abstract: Epigenetic modifications on natural chromosomes are inherited and maintained in a default state, making it challenging to remove intrinsic marks to study the fundamental principles of their establishment and further influence on transcriptional regulation. In this study, we developed SynNICE, a method for assembling and delivering intact, naive, synthetic megabase (Mb)-scale human DNA into early mouse embryos, to study de novo epigenetic regulation. By assembling and delivering a 1.14-Mb human AZFa (hAZFa) locus, we observed the spontaneous incorporation of murine histones and the establishment of DNA methylation at the one-cell stage. Notably, DNA methylation from scratch strongly enriches at repeat sequences without H3K9me3 reinforcement. Furthermore, the transcription of hAZFa initiated at the four-cell stage is regulated by newly established DNA methylation. This method provides a unique platform for exploring de novo epigenomic regulation mechanisms in higher animals.

DOI: 10.1038/s41592-025-02746-8

Source: https://www.nature.com/articles/s41592-025-02746-8