17 / 2024-09-06 14:39:01

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

3D interaction,ZGA

Zygotic genome activation (ZGA) represents the inaugural post-fertilization transcription event. In the early onset of ZGA species like mouse (during 2-cell stage), RNA polymerase II (Pol II) initiates ZGA through a stepwise transition, but this process remains unclear in late ZGA species, such as bovine and human (during 4-8 cell stage). Here, profiling Pol II in bovine revealed strong intergenic Pol II clusters, termed super Pol II domains (SPDs), that boosted minor ZGA gene expression via chromatin interactions. Perturbation of SPDs using CRISPRi in bovine embryos decreased the expression of two minor ZGA genes, KLF17 or DUXA, and knocking down these genes also led to aberrant ZGA and impeded bovine embryogenesis. Intriguingly, a similar strategy was observed in human embryos to rapidly enhance the expression of minor ZGA genes. In contrast, these genes are precociously expressed in porcine and mouse oocytes, and do not require the SPD-mediated regulation for the ZGA process during embryonic development. Our findings highlight SPD enhancement as a specific adaptation in bovine and human embryos to transcript comparable minor ZGA products as mammals with early ZGA, thus illustrating a previously underappreciated strategy for embryonic development in late ZGA mammals.