英国弗朗西斯·克里克研究所James M. A. Turner小组的一项最新研究发现有袋动物和真动物胚胎中不同的DNA甲基化动力学。相关论文发表在2025年5月14日出版的《自然》杂志上。

为了解决这个问题，研究组在一种有袋动物——负鼠（Monodelphis domestica）的配子、胚胎和成年组织中生成了碱基分辨率的DNA甲基化图谱，揭示了来自真动物模型的变异。卵母细胞和精子之间DNA甲基化水平的差异不像真动物那样明显。

此外，与真动物的基因组不同，负鼠的基因组在卵裂阶段仍然高度甲基化。在胚泡中，DNA去甲基化在外胚层中是短暂的和适度的。

然而，它被保存在滋养外胚层中，这表明在哺乳动物胎盘中DNA低甲基化具有进化保守的功能。

此外，与真动物不同的是，在胚胎发生过程中，失活的X染色体整体DNA低甲基化。研究团队鉴定出配子不同的甲基化区域，这些区域在胚胎中表现出不同的命运，其中一些是短暂的，另一些是保留的，代表了候选的印迹位点。该团队还揭示了印迹X失活的可能机制，通过母体DNA甲基化的xist样非编码RNA RSX11。该研究团队得出结论，进化上不同的真动物和有袋动物在胚胎发生时的DNA去甲基化是不同的。

据悉，基于对胎盘物种（eutherians）的开创性研究，已经出现了哺乳动物发育的范式，其中胚胎发生需要全基因组消除亲本DNA甲基化。事实上，这种DNA甲基化重编程是否在其他哺乳动物中保守尚不清楚。

附：英文原文

Title: Divergent DNA methylation dynamics in marsupial and eutherian embryos

Author: Leeke, Bryony J., Varsally, Wazeer, Ogushi, Sugako, Zohren, Jasmin, Menchero, Sergio, Courtois, Aurlien, Snell, Daniel M., Teissandier, Aurlie, Ojarikre, Obah, Mahadevaiah, Shantha K., Decarpentrie, Fanny, Oakey, Rebecca J., VandeBerg, John L., Turner, James M. A.

Issue&Volume: 2025-05-14

Abstract: Based on seminal work in placental species (eutherians)1,2,3,4,5,6,7,8,9,10, a paradigm of mammalian development has emerged wherein the genome-wide erasure of parental DNA methylation is required for embryogenesis. Whether such DNA methylation reprogramming is, in fact, conserved in other mammals is unknown. Here, to resolve this point, we generated base-resolution DNA methylation maps in gametes, embryos and adult tissues of a marsupial, the opossum Monodelphis domestica, revealing variations from the eutherian-derived model. The difference in DNA methylation level between oocytes and sperm is less pronounced than that in eutherians. Furthermore, unlike the genome of eutherians, that of the opossum remains hypermethylated during the cleavage stages. In the blastocyst, DNA demethylation is transient and modest in the epiblast. However, it is sustained in the trophectoderm, suggesting an evolutionarily conserved function for DNA hypomethylation in the mammalian placenta. Furthermore, unlike that in eutherians, the inactive X chromosome becomes globally DNA hypomethylated during embryogenesis. We identify gamete differentially methylated regions that exhibit distinct fates in the embryo, with some transient, and others retained and that represent candidate imprinted loci. We also reveal a possible mechanism for imprinted X inactivation, through maternal DNA methylation of the Xist-like noncoding RNA RSX11. We conclude that the evolutionarily divergent eutherians and marsupials use DNA demethylation differently during embryogenesis.

DOI: 10.1038/s41586-025-08992-2

Source: https://www.nature.com/articles/s41586-025-08992-2