RIF1 regulates post-replicative H3K9me3 restoration at multiple cell cycle stages

The kinetics of restoration of these marks on the newly incorporated histones dictates how quickly genomic domains re-acquire their epigenetic identity after replication. H3K9me3 is reconstituted extremely slowly: only in the following S-phase, just prior to replication, the pre-replication levels are restored.

The molecular mechanisms behind this slow reconstitution are unknown. We show here that RIF1 reassociation with heterochromatin during mitotic exit is required to set up a chromatin permissive for histone methyltransferases to resume H3K9me3 deposition. RIF1 facilitates the recruitment of SUV39H1, HP1a and HP1b and is required for the increased tri-methylation of H3K9 that takes place during G1.