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.

受精卵的表观遗传重编程涉及组蛋白变体 H3.3 的动态掺入。然而，H3.3 在早期发育过程中的全基因组分布和动态仍然未知。在这里，我们描绘了小鼠卵母细胞和早期胚胎中的 H3.3 景观。我们出乎意料地在成熟卵母细胞和受精卵中发现了一种非规范的 H3.3 模式，其中 H3.3 在活性染色质处的局部富集受到抑制，并且 H3.3 在整个基因组中分布相对均匀。有趣的是，虽然非规范 H3.3 模式在卵子发生过程中逐渐形成，但它在双细胞阶段以不依赖转录和依赖复制的方式迅速转变为规范模式。我们发现由染色质组装因子 CAF-1 介导的 H3.1/H3.2 的掺入是从头建立规范模式的关键过程。