Yuan Shenli, Zhan Jianhong, Zhang Jingye, Liu Zhenbo, Hou Zhenzhen, Zhang Chuanxin, Yi Lizhi, Gao Lei, Zhao Han, Chen Zi-Jiang, Liu Jiang, Wu Keliang
Center for Reproductive Medicine, Shandong University, Jinan, Shandong, China.
CAS Key Laboratory of Genome Sciences and Information, Collaborative Innovation Center of Genetics and Development, Beijing Institute of Genomics, and China National Center for Bioinformation, Chinese Academy of Sciences, Beijing, China.
Cell Discov. 2023 Jan 31;9(1):13. doi: 10.1038/s41421-022-00494-z.
Although parental genomes undergo extensive epigenetic reprogramming to be equalized after fertilization, whether they play different roles in human zygotic genome activation (ZGA) remains unknown. Here, we mapped parental transcriptomes by using human parthenogenetic (PG) and androgenetic (AG) embryos during ZGA. Our data show that human ZGA is launched at the 8-cell stage in AG and bi-parental embryos, but at the morula stage in PG embryos. In contrast, mouse ZGA occurs at the same stage in PG and AG embryos. Mechanistically, primate-specific ZNF675 with AG-specific expression plays a role in human ZGA initiated from paternal genome at the 8-cell stage. AG-specifically expressed LSM1 is also critical for human maternal RNA degradation (MRD) and ZGA. The allelic expressions of ZNF675 and LSM1 are associated with their allelically epigenetic states. Notably, the paternally specific expressions of ZNF675 and LSM1 are also observed in diploid embryos. Collectively, human ZGA is initiated from paternal genome.
尽管亲代基因组在受精后会经历广泛的表观遗传重编程以实现均等化，但它们在人类合子基因组激活（ZGA）中是否发挥不同作用仍不清楚。在这里，我们通过在ZGA期间使用人类孤雌生殖（PG）和孤雄生殖（AG）胚胎来绘制亲代转录组图谱。我们的数据表明，人类ZGA在AG胚胎和双亲胚胎的8细胞阶段启动，但在PG胚胎的桑椹胚阶段启动。相比之下，小鼠ZGA在PG和AG胚胎的同一阶段发生。从机制上讲，具有AG特异性表达的灵长类特异性ZNF675在8细胞阶段从父本基因组启动的人类ZGA中发挥作用。AG特异性表达的LSM1对人类母体RNA降解（MRD）和ZGA也至关重要。ZNF675和LSM1的等位基因表达与其等位基因表观遗传状态相关。值得注意的是，在二倍体胚胎中也观察到ZNF675和LSM1的父本特异性表达。总体而言，人类ZGA是从父本基因组启动的。
