Polycomb repressor complex 1 (PRC1) proteins remain bound to chromatin during DNA replication, reports a new study in Cell. This finding suggests that the retention of chromatin regulatory proteins throughout DNA replication might be an important mechanism of epigenetic inheritance.

Chromatin templates that are bound by the PRC1 core complex (PCC) prior to DNA replication are completely replicated in vitro. Notably, the known inhibitory effect of PCC on chromatin remodelling persists through chromatin replication. So, PCC binds to, and affects, chromatin through DNA replication in vitro.

Polycomb repressor complex 1 (PRC1) proteins remain bound to chromatin during DNA replication...

Using a modified chromatin immunoprecipitation assay, Francis et al. found that PCC is bound to both replicated and unreplicated DNA. Further experiments suggest that PCC is not released from templates during replication.

Given that PRC1 can bind to the repressive mark trimethylated histone H3 Lys27 (H3K27me3), it has been proposed that the transfer of H3K27me3 to daughter DNA during DNA replication might recruit PRC1 if this complex is disrupted by the passage of the replication fork. However, Francis et al. found that H3K27me3 is not required for maintaining the association of PCC with chromatin during DNA replication.

Using chromatin immunoprecipitation, the authors observed that PCC components colocalize with bromodeoxyuridine (BrdU, a nucleotide analogue that incorporates into newly synthesized DNA) at Polycomb response elements (PREs) in Drosophila melanogaster S2 cells undergoing S phase. Interestingly, the amount of a PCC component — posterior sex comb (PSC) — that is bound to BrdU-labelled PRE increases after DNA replication.

These data support a model in which PCC bound to DNA before DNA replication is maintained on the daughter DNA template, and additional PCC is added to the daughter DNA template after DNA replication is completed to restore the full amount of PCC required for silencing.