Recycling of modified H2A-H2B provides short-term memory of chromatin states

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. [Display omitted] •Histone H2A-H2B are recycled during DNA replication independent of H3-H4•H2A.Z and H2BK120ub1 mark nascent chromatin prior to transcription re-start•H2A-H2B modification and variant landscapes are restored rapidly after replication•H2AK119ub1 facilitates accurate and timely restoration of H3K27me3 post-replication Accurate recycling of histones during DNA replication is crucial for restoring chromatin landscape and cell identity. A new study provides mechanistic insights into the elusive replication-dependent recycling of H2A-H2B and the associated histone modifications.