近日，中国科学院动物研究所郭帆等研究人员合作发现，人类胚胎植入前发育过程中亲本5-羟甲基胞嘧啶的不同动态调节早期谱系基因的表达。这一研究成果于2024年7月30日在线发表在国际学术期刊《自然—细胞生物学》上。

研究人员发现早期人类胚胎从卵母细胞继承了大量5-羟甲基胞嘧啶（5hmC），这些5hmC在胚胎发育过程中意外地经历了去从头羟甲基化。此外，受精后父源基因组中的5hmC生成大致遵循母源模式，这与DNA甲基化动态及持续甲基化区域相关。5hmC持续存在直到八细胞阶段，并在OTX2结合位点表现出高度富集，而OTX2在人体胚胎中的敲低则影响了早期谱系基因的表达。

具体而言，5hmC的缺失影响了胚胎基因的激活，这通过在早期人类胚胎中异位表达小鼠Tet3进一步评估。这些发现揭示了5hmC的独特动态，并揭示了其在早期人类胚胎发育中的多面功能。

据悉，DNA的5-甲基胞嘧啶（5mC）转化为5hmC由TET酶所催化，这代表了一种重要的表观遗传修饰，但其在早期人类胚胎中的作用仍然基本未知。

附：英文原文

Title: Distinct dynamics of parental 5-hydroxymethylcytosine during human preimplantation development regulate early lineage gene expression

Author: Liang, Dan, Yan, Rui, Long, Xin, Ji, Dongmei, Song, Bing, Wang, Mengyao, Zhang, Fan, Cheng, Xin, Sun, Fengyuan, Zhu, Ran, Hou, Xinling, Wang, Tianjuan, Zou, Weiwei, Zhang, Ying, Pu, Zhixin, Zhang, Jing, Zhang, Zhiguo, Liu, Yajing, Hu, Yuqiong, He, Xiaojin, Cao, Yunxia, Guo, Fan

Issue&Volume: 2024-07-30

Abstract: The conversion of DNA 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) by TET enzymes represents a significant epigenetic modification, yet its role in early human embryos remains largely unknown. Here we showed that the early human embryo inherited a significant amount of 5hmCs from an oocyte, which unexpectedly underwent de novo hydroxymethylation during its growth. Furthermore, the generation of 5hmC in the paternal genome after fertilization roughly followed the maternal pattern, which was linked to DNA methylation dynamics and regions of sustained methylation. The 5hmCs persisted until the eight-cell stage and exhibited high enrichment at OTX2 binding sites, whereas knockdown of OTX2 in human embryos compromised the expression of early lineage genes. Specifically, the depletion of 5hmC affected the activation of embryonic genes, which was further evaluated by ectopically expressing mouse Tet3 in human early embryos. These findings revealed distinct dynamics of 5hmC and unravelled its multifaceted functions in early human embryonic development.

DOI: 10.1038/s41556-024-01475-y

Source: https://www.nature.com/articles/s41556-024-01475-y