ZFIN ID: ZDB-PUB-150107-9
Regulation of zygotic genome activation and DNA damage checkpoint acquisition at the mid-blastula transition
Zhang, M., Kothari, P., Mullins, M., Lampson, M.A.
Date: 2014
Source: Cell cycle (Georgetown, Tex.)   13: 3828-38 (Journal)
Registered Authors: Mullins, Mary C.
Keywords: MBT, Mid-blastula Transition, ZGA, Zygotic genome activation, cell cycle checkpoints, embryogenesis, mid-blastula transition, zygotic genome activation
MeSH Terms:
  • Animals
  • Blastula/metabolism*
  • Blastula/radiation effects
  • Cell Cycle Checkpoints/drug effects
  • Cell Cycle Checkpoints/radiation effects
  • Checkpoint Kinase 2/genetics
  • Checkpoint Kinase 2/metabolism
  • DNA Breaks, Double-Stranded/drug effects
  • DNA Breaks, Double-Stranded/radiation effects
  • DNA Repair
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/metabolism
  • Gamma Rays
  • Genome*
  • Histones/metabolism
  • Hydroxyurea/toxicity
  • Protein Kinases/genetics
  • Protein Kinases/metabolism
  • Recombinant Fusion Proteins/biosynthesis
  • Recombinant Fusion Proteins/genetics
  • Signal Transduction
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 25558827 Full text @ Cell Cycle
Following fertilization, oviparous embryos undergo rapid, mostly transcriptionally silent cleavage divisions until the mid-blastula transition (MBT), when large-scale developmental changes occur, including zygotic genome activation (ZGA) and cell cycle remodeling, via lengthening and checkpoint acquisition. Despite their concomitant appearance, whether these changes are co-regulated is unclear. Three models have been proposed to account for the timing of (ZGA). One model implicates a threshold nuclear to cytoplasmic (N:C) ratio, another stresses the importance cell cycle elongation, while the third model invokes a timer mechanism. We show that precocious Chk1 activity in pre-MBT zebrafish embryos elongates cleavage cycles, thereby slowing the increase in the N:C ratio. We find that cell cycle elongation does not lead to transcriptional activation. Rather, ZGA slows in parallel with the N:C ratio. We show further that the DNA damage checkpoint program is maternally supplied and independent of ZGA. Although pre-MBT embryos detect damage and activate Chk2 after induction of DNA double-strand breaks, the Chk1 arm of the DNA damage response is not activated, and the checkpoint is nonfunctional. Our results are consistent with the N:C ratio model for ZGA. Moreover, the ability of precocious Chk1 activity to delay pre-MBT cell cycles indicate that lack of Chk1 activity limits checkpoint function during cleavage cycles. We propose that Chk1 gain-of-function at the MBT underlies cell cycle remodeling, whereas ZGA is regulated independently by the N:C ratio.