Chromatin landscapes are disrupted during DNA replication and must be restored faithfully to maintain genome regulation and cell identity. The histone H3-H4 modification landscape is restored by parental histone recycling and modification of new histones. How DNA replication impacts on histone H2A-H2B is currently unknown. Here, we measure H2A-H2B modifications and H2A.Z during DNA replication and across the cell cycle using quantitative genomics. We show that H2AK119ub1, H2BK120ub1, and H2A.Z are recycled accurately during DNA replication. Modified H2A-H2B are segregated symmetrically to daughter strands via POLA1 on the lagging strand, but independent of H3-H4 recycling. Post-replication, H2A-H2B modification and variant landscapes are quickly restored, and H2AK119ub1 guides accurate restoration of H3K27me3. This work reveals epigenetic transmission of parental H2A-H2B during DNA replication and identifies cross talk between H3-H4 and H2A-H2B modifications in epigenome propagation. We propose that rapid short-term memory of recycled H2A-H2B modifications facilitates restoration of stable H3-H4 chromatin states.

染色质景观在 DNA 复制过程中被破坏，必须忠实地恢复以维持基因组调控和细胞身份。组蛋白 H3-H4 修饰景观通过亲代组蛋白回收和新组蛋白修饰得到恢复。DNA 复制如何影响组蛋白 H2A-H2B 目前尚不清楚。在这里，我们使用定量基因组学测量 DNA 复制期间和跨细胞周期的 H2A-H2B 修饰和 H2A.Z。我们表明 H2AK119ub1、H2BK120ub1 和 H2A.Z 在 DNA 复制过程中被准确回收。修饰的 H2A-H2B 通过滞后链上的 POLA1 与子链对称分离，但与 H3-H4 循环无关。复制后，H2A-H2B 修改和变异景观快速恢复，H2AK119ub1 指导 H3K27me3 的准确恢复。这项工作揭示了 DNA 复制过程中亲代 H2A-H2B 的表观遗传传递，并确定了表观基因组传播中 H3-H4 和 H2A-H2B 修饰之间的串扰。我们提出，回收的 H2A-H2B 修饰的快速短期记忆有助于恢复稳定的 H3-H4 染色质状态。