Super RNA Pol II domains enhance minor ZGA through 3D interaction to ensure the integrity of major transcriptional waves in late-ZGA mammals
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.
Authors
- Hengkuan Li
- Mei Jiao
- Zhangyuan Pan (ORCID: https://orcid.org/0000-0001-5394-3203)
- Benjamin C. Carter (ORCID: https://orcid.org/0000-0001-6530-9568)
- Hexu Zhang
- Wenying Li (ORCID: https://orcid.org/0000-0002-7104-3505)
- Gang Ren (ORCID: https://orcid.org/0000-0001-9690-5995)
- Jie Wu (ORCID: https://orcid.org/0000-0002-9865-180X)
- Linjie Song
- Shuhong Zhao (ORCID: https://orcid.org/0000-0002-3997-2320)
- Binqiang Shi
- Zixiao Liu (ORCID: https://orcid.org/0000-0002-7927-9336)
- Xin Liu (ORCID: https://orcid.org/0000-0002-0011-6113)
- Yong Zhang (ORCID: https://orcid.org/0009-0009-2943-544X)
- Yong Wang (ORCID: https://orcid.org/0000-0003-3744-912X)
- Yunxia Zhao
- Zhenyu Dong (ORCID: https://orcid.org/0009-0003-4507-8493)
- Jingcheng Zhang (ORCID: https://orcid.org/0000-0001-5167-4003)
- Mingyang Hu (ORCID: https://orcid.org/0000-0002-4367-0384)
- Debao Wang (ORCID: https://orcid.org/0000-0002-1978-2714)
- Chuan Zhou (ORCID: https://orcid.org/0000-0002-5972-1975)
- Linmi Li
Institutions
- Huazhong Agricultural University (CN)
- Chinese Academy of Agricultural Sciences (CN)
- Hunan Agricultural University (CN)
- Northwest A&F University (CN)
- Ministry of Agriculture, Livestock, and Food Supply (BR)
Publication Details
- Journal
- Cell Genomics
- Published
- 2025-05-01
- DOI
- https://doi.org/10.1016/j.xgen.2025.100856
- Citations
- 7
- Primary Topic
- Genomics and Chromatin Dynamics
- Type
- article
- Field-Weighted Citation Impact
- 5.64
Funders
- National Natural Science Foundation of China
- Ministry of Agriculture and Rural Affairs of the People's Republic of China
- Key Science and Technology Program of Shaanxi Province