Profiling DNA Replication Timing in Zebrafish Embryos Reveals Dynamic Regulation During Development

The temporal order of DNA replication is modified during differentiation, but when a replication timing program is established and what alterations occur in vivo during embryogenesis are not known. Here we used zebrafish embryos to generate genome-wide, high-resolution replication timing maps throughout development. Unexpectedly, a non-random and defined replication timing program was evident in the rapid cell cycles before the midblastula transition. The majority of the genome undergoes dynamic shifts in replication timing throughout development as the timing program is decompressed, with many abrupt timing changes occurring during lineage specification. Strikingly, the long arm of chromosome 4 undergoes a developmentally regulated switch to late replication, reminiscent of mammalian X chromosome inactivation. This analysis also revealed a strong relationship between early replication and epigenetic marks at enhancers. Collectively, these data reveal the major changes in replication timing that occur during zebrafish embryogenesis, and demonstrate its dynamic regulation during vertebrate development. Examination of DNA replication timing at six developmental timepoints