The chromatin backdrop of DNA replication: Lessons from genetics and genome-scale analyses

The entire cellular genome must replicate during each cell cycle, but it is yet unclear how replication proceeds along with chromatin condensation and remodeling while ensuring the fidelity of the replicated genome. Mapping replication initiation sites can provide clues for the coordination of DNA replication and transcription on a whole-genome scale. Here we discuss recent insights obtained from genome-scale analyses of replication initiation sites and transcription in mammalian cells and ask how transcription and chromatin modifications affect the frequency of replication initiation events. We also discuss DNA sequences, such as insulators and replicators, which modulate replication and transcription of target genes, and use genome-wide maps of replication initiation sites to evaluate possible commonalities between replicators and chromatin insulators. This article is part of a Special Issue entitled: Chromatin in time and space.

► Genome-scale maps and genetic analyses probe how replication coordinates with transcription.
► Replication starts preferentially at accessible chromatin and at methylated CpG regions.
► Replication starts at regions that straddle but do not overlap transcription start site.
► Replication starts preferentially at moderate, but not highly transcribed, chromatin regions.
► DNA sequences that start replication might colocalize with chromatin insulators.