DNA replication timing during development anticipates transcriptional programs and parallels enhancer activation

Genome Research
Joseph C SiefertChristopher L Sansam

Abstract

In dividing cells, DNA replication occurs in a precise order, but many questions remain regarding the mechanisms of replication timing establishment and regulation. We now have generated genome-wide, high-resolution replication timing maps throughout zebrafish development. Unexpectedly, in the rapid cell cycles preceding the midblastula transition, a defined timing program was present that predicted the initial wave of zygotic transcription. Replication timing was thereafter progressively and continuously remodeled across the majority of the genome, and epigenetic changes involved in enhancer activation frequently paralleled developmental changes in replication timing. The long arm of Chromosome 4 underwent a dramatic developmentally regulated switch to late replication during gastrulation, reminiscent of mammalian X Chromosome inactivation. This study reveals that replication timing is dynamic and tightly linked to epigenetic and transcriptional changes throughout early zebrafish development. These data provide insight into the regulation and functions of replication timing and will enable further mechanistic studies.

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Citations

Sep 4, 2019·Nature Reviews. Molecular Cell Biology·Claire MarchalDavid M Gilbert
Dec 19, 2019·Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology·Michelle L HulkeAmnon Koren
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Aug 11, 2021·The Journal of Biological Chemistry·Weiyan JiaRandal S Tibbetts
Oct 6, 2021·Cell Reports·Capucine Van RechemJohnathan R Whetstine

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