Resetting histone modifications during human parental-to-zygotic transition

Histone modifications regulate gene expression and development. To address how they are reprogrammed in human early development, we investigated key histone marks in human oocytes and early embryos. Unlike that in mouse, the permissive mark H3K4me3 largely exhibits canonical patterns at promoters in human oocytes. After fertilization, pre-zygotic genome activation (ZGA) embryos acquire permissive chromatin and widespread H3K4me3 in CpG-rich regulatory regions. By contrast, the repressive mark H3K27me3 undergoes global depletion. CpG-rich regulatory regions then resolve to either active or repressed states upon ZGA, followed by subsequent restoration of H3K27me3 at developmental genes. Finally, through combining chromatin and transcriptome maps, we revealed transcription circuitry and asymmetric H3K27me3 patterning during early lineage specification. Collectively, our data unveil a priming phase connecting human parental-to-zygotic epigenetic transition. Overall design: We investigated the dynamics of two key histone marks H3K4me3, H3K27me3 in human oocytes and pre-implantation embryos, and H3K27ac in post-ZGA embryos using CUT&RUN.