Replication timing and epigenetic reprogramming of gene expression: a two-way relationship?

An overall link between the potential for gene transcription and the timing of replication in S phase is now well established in metazoans. Here we discuss emerging evidence that highlights the possibility that replication timing is causally linked with epigenetic reprogramming. In particular, we bring together conclusions from a range of studies to propose a model in which reprogramming factors determine the timing of replication and the implementation of reprogramming events requires passage through S phase. These considerations have implications for our understanding of development, evolution and diseases such as cancer.