Histone H1 facilitates restoration of H3K27me3 during DNA replication by chromatin compaction

Here we adopt ChOR-seq (Chromatin Occupancy after Replication) to monitor the dynamic re-establishment of H3K27me3 on nascent DNA during DNA replication. We found that the linker histone H1 facilitates the rapid post-replication restoration of H3K27me3 on repressive genes, which is essential for maintaining gene silencing and cell identity during cell division. Interestingly, the restoration rate of H3K27me3 on nascent DNA is greatly compromised after depletion of H1c/d/e. Finally, our in vitro biochemical experiments demonstrate that H1 facilitates the propagation of H3K27me3 by PRC2 through compacting chromatin. Collectively, our results indicate that H1-mediated chromatin compaction facilitates the propagation and restoration of H3K27me3 after DNA replication, which is key to cell fate determination. Overall design: ChOR-seq, ChIP-seq and RNA-seq for WT and H1TKO cells