RT Journal
A1 Siefert, Joseph C.
A1 Georgescu, Constantin
A1 Wren, Jonathan D.
A1 Koren, Amnon
A1 Sansam, Christopher L.
T1 DNA replication timing during development anticipates transcriptional programs and parallels enhancer activation
JF Genome Research 
JO Genome Research 
YR 2017 
FD August 01 
VO 27 
IS 8 
SP 1406 
OP 1416 
DO 10.1101/gr.218602.116 
UL http://genome.cshlp.org/content/27/8/1406.abstract 
AB 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.