Specialized replication of heterochromatin domains ensures self-templated chromatin assembly and epigenetic inheritance [ChIP-seq]
Heterochromatin domains defined by distinct histone methylation patterns are a major feature of mammalian genomes. Epigenetic pathways ensure stable heterochromatin inheritance through cell division to prevent the expression of lineage-inappropriate genes and defects in this process can lead to many diseases including cancer. Previous studies have shown that heterochromatin maintenance requires a critical threshold of methylated histones, but how modified parental histones are transferred to daughter strands during DNA replication is unclear. We find that heterochromatin domains are specialized replication zones enriched in replisome components, which load factors that help retain parental histones. This mechanism is further supported by the boundary elements surrounding the heterochromatin domains. DNA replication is thus coordinated with histone preservation to facilitate epigenetic inheritance of heterochromatin. Overall design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for the proteins Mcl1, Mcm2 and Rix1, the BrdU analogue, and the lysine 9 trimethylated histone H3 in fission yeast. Input control and immunoprecipitation samples are provided for each experiment.