Global early replication disrupts gene expression and chromatin conformation in a single cell cycle

The early embryonic divisions of many organisms, including fish, flies and frogs are characterised by a very rapid S-phase caused by high rates of replication initiation. In somatic cells, S-phase is much longer due to both a reduction in the total number of initiation events and the imposition of a temporal order of origin activation. The physiological importance of changes in the rate and timing of replication initiation in S-phase remains unclear. Here we assess the importance of the temporal control of replication initiation using a conditional system in budding yeast to drive the early replication of all origins in a single cell cycle. We show that global early replication disrupts the expression of over a quarter of all genes. By deleting individual origins, we show that delaying replication is sufficient to restore normal gene expression, directly establishing replication timing control in this regulation. Global early replication disrupts nucleosome positioning and transcription factor binding during S-phase, suggesting that the rate of S-phase is important to regulate the chromatin landscape. Together these data provide new insight into the role of a temporal order of origin firing for coordinating replication, gene expression and chromatin establishment as occurs in the early embryo.