Super RNA Pol II domains enhance minor ZGA through 3D interaction to ensure the integrity of major transcriptional waves in late-ZGA mammals

作者：Jingcheng Zhang, Hengkuan Li, Linmi Li, Jie Wu, Linjie Song, Xin Liu, Zhangyuan Pan, Chuan Zhou, Wenying Li, Zixiao Liu, Mei Jiao, Mingyang Hu, Zhenyu Dong, Hexu Zhang, Binqiang Shi, Yong Wang, Debao Wang, Benjamin C. Carter, Shuhong Zhao, Gang Ren, Yunxia Zhao, Yong Zhang · 发表于：Cell Genomics · 年份：2025 · DOI：10.1016/j.xgen.2025.100856 · 被引用次数：10 · 研究领域：Genomics and Chromatin Dynamics、RNA Research and Splicing、RNA modifications and cancer

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.