Genomic uracil in early embryonic development of Zebrafish

Here, we report an unexpectedly high uracil content in early Danio rerio embryos, which decreases markedly by the time of zygotic genome activation (ZGA). Genome-wide profiling of U-DNA at 2.5 hpf revealed enrichment at specific satellite repeats, including MOSAT, BRSAT1, and SAT-12.

These observations suggest that U-DNA and its processing could play roles either in supporting rapid cleavage divisions or in facilitating chromatin remodeling required for ZGA. To test this, we microinjected fertilized eggs with either active or catalytically inactive uracil-DNA glycosylase (UNG), thereby promoting or inhibiting U-DNA removal. Both interventions resulted in embryonic lethality, consistent with disruption of the normal uracil-processing balance and consequent perturbation of ZGA timing.