The delicate relationship between DNA replication timing and gene expression

The order in which different domains of DNA undergo replication forms a highly regulated, precise pattern. Replication timing (RT) has been studied at a variety of resolutions and can now be mapped in a genome-wide fashion. RT is correlated with a plethora of genetic and epigenetic features, and here, we highlight recent developments in our understanding of the relationship between RT and transcription. In spite of the general correlation between early replication and transcription, recent single-cell experiments and detailed time-course models indicate that the correlation is not absolute. Moreover, asynchronous replicating regions are associated with monoallelic expressed genes, but the active allele is not always the early one. We propose that RT contributes to transcription at a few levels but that it is not a prerequisite for it.