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

Epigenetic reprogramming of the zygote involves dynamic incorporation of the 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, while the non-canonical H3.3 pattern forms gradually during oogenesis, it quickly switches to a canonical pattern at the 2-cell stage in a transcription-independent and replication-dependent manner. We find that incorporation of H3.1/H3.2 mediated by 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. H3.3 ChIP-seq was performed with mouse oocytes, early embryos and mESCs. H3.1/H3.2 CUT&RUN was performed with 2-cell embryos, and H3.3 CUT&RUN was performed with mESCs. RNA-seq was performed with 8-cell embryos or blastocysts.