Reprogramming of the histone H3.3 landscape in the early mouse embryo

Epigenetic reprogramming of the zygote involves dynamic incorporation of histone variant H3.3. However, the genome-wide distribution and dynamics of H3.3 during early development remain unknown. Here, we delineate the H3.3 landscapes in mouse oocytes and early embryos. We unexpectedly identify a non-canonical H3.3 pattern in mature oocytes and zygotes, in which local enrichment of H3.3 at active chromatin is suppressed and H3.3 is relatively evenly distributed across the genome. Interestingly, although the non-canonical H3.3 pattern forms gradually during oogenesis, it quickly switches to a canonical pattern at the two-cell stage in a transcription-independent and replication-dependent manner. We find that incorporation of H3.1/H3.2 mediated by chromatin assembly factor CAF-1 is a key process for the de novo establishment of the canonical pattern. Our data suggest that the presence of the non-canonical pattern and its timely transition toward a canonical pattern support the developmental program of early embryos. Ultra-low-input native ChIP-seq analyses of genome-wide histone H3.3 distribution during early mouse development reveal a CAF-1-dependent transition from a non-canonical pattern in the oocyte and zygote to a canonical distribution at the two-cell stage.

Automated summary

Epigenetic reprogramming of the zygote involves the dynamic incorporation of histone variant H3.3, with a non-canonical pattern present in mature oocytes and zygotes transitioning to a canonical pattern at the two-cell stage. This transition is facilitated by the chromatin assembly factor CAF-1 mediating the incorporation of H3.1/H3.2.