ZFIN ID: ZDB-PUB-170518-7
DNA replication timing during development anticipates transcriptional programs and parallels enhancer activation
Siefert, J.C., Georgescu, C., Wren, J.D., Koren, A., Sansam, C.L.
Date: 2017
Source: Genome research   27(8): 1406-1416 (Journal)
Registered Authors: Sansam, Chris, Siefert, Joseph
Keywords: none
Microarrays: GEO:GSE85713
MeSH Terms:
  • Animals
  • DNA Replication Timing*
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/metabolism*
  • Enhancer Elements, Genetic*
  • Gene Expression Regulation, Developmental*
  • Genome
  • High-Throughput Nucleotide Sequencing/methods
  • Transcription, Genetic*
  • Zebrafish/genetics*
  • Zebrafish/growth & development*
PubMed: 28512193 Full text @ Genome Res.
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. Strikingly, 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.