Zhang Jingcheng, Li Hengkuan, Li Linmi, Wu Jie, Song Linjie, Liu Xin, Pan Zhangyuan, Zhou Chuan, Li Wenying, Liu Zixiao, Jiao Mei, Hu Mingyang, Dong Zhenyu, Zhang Hexu, Shi Binqiang, Wang Yong, Wang Debao, Carter Benjamin, Zhao Shuhong, Ren Gang, Zhao Yunxia, Zhang Yong
Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling 712100, China.
Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling 712100, China; Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education and Key Laboratory of Swine Genetics and Breeding of Ministry of Agriculture, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
Cell Genom. 2025 Apr 29:100856. doi: 10.1016/j.xgen.2025.100856.
Zygotic genome activation (ZGA) occurs at distinct stages across mammals, with mice initiating ZGA at the 2-cell stage and bovines and humans activating the process in the 4- to 8-cell stages. RNA polymerase II (RNA Pol II) gradually initiates ZGA in mice, but regulation in late-ZGA species remains unclear. Here, RNA Pol II profiling in bovine embryos identified strong intergenic clusters that boost minor ZGA gene expression via chromatin interactions and are named super RNA Pol II domains (SPDs). CRISPRi perturbation of SPDs in bovine embryos decreases the expression of minor ZGA genes, whereas the knockdown of these genes disrupts major ZGA and embryogenesis. Rapid enhancement of minor ZGA genes also occurs in human embryos. Alternatively, mouse and porcine oocytes precociously express these minor ZGA genes without SPDs. Thus, SPDs appear to be an adaptation in bovine embryos, promoting minor ZGA gene expression to comparable levels as early-ZGA species, illuminating species-specific regulation of ZGA timing.
合子基因组激活（ZGA）在不同哺乳动物中发生于不同阶段，小鼠在二细胞阶段启动ZGA，而牛和人类则在4至8细胞阶段激活这一过程。RNA聚合酶II（RNA Pol II）在小鼠中逐渐启动ZGA，但晚期ZGA物种中的调控机制仍不清楚。在此，对牛胚胎中的RNA Pol II进行分析，发现了强大的基因间簇，这些基因间簇通过染色质相互作用促进次要ZGA基因表达，被命名为超级RNA Pol II结构域（SPD）。对牛胚胎中SPD进行CRISPRi干扰会降低次要ZGA基因的表达，而敲低这些基因则会破坏主要ZGA和胚胎发育。在人类胚胎中也会快速增强次要ZGA基因的表达。另外，小鼠和猪的卵母细胞会过早表达这些没有SPD的次要ZGA基因。因此，SPD似乎是牛胚胎中的一种适应性变化，将次要ZGA基因的表达提升到与早期ZGA物种相当的水平，揭示了ZGA时间的物种特异性调控。
