|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.
|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|
|PubMed:||25558827 Full text @ Cell Cycle|
Zhang, M., Kothari, P., Mullins, M., Lampson, M.A. (2014) Regulation of zygotic genome activation and DNA damage checkpoint acquisition at the mid-blastula transition. Cell cycle (Georgetown, Tex.). 13:3828-38.
ABSTRACTFollowing 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.