The reprogramming and function of H4K20me1 during early embryo development

Histone modifications play critical roles in regulating chromatin dynamics and embryonic development. Among these, histone H4 lysine 20 mono-methylation (H4K20me1) is an essential epigenetic mark associated with gene expression and genome stability. However, the reprogramming and functional roles of H4K20me1 in early embryogenesis remain unclear. Here, we map genome-wide distributions of H4K20me1 in mouse, human, and zebrafish early embryos, revealing a broad distribution pattern along with species-specific features. H4K20me1 is predominantly enriched in gene bodies and undergoes dynamic erasure and reestablishment following fertilization. Functional perturbation of SET8, the only known H4K20me1 methyltransferase, results in developmental arrest, highlighting its necessity for embryogenesis. Mechanistically, H4K20me1 is crucial for zygotic genome activation (ZGA), where it regulates RNA synthesis and transcription, and promotes chromatin accessibility. Our findings provide insights into the dynamic reprogramming and regulatory functions of H4K20me1 in early developmental processes.