Document Type
Article
Abstract
During early development, embryos undergo the maternal-to-zygotic transition (MZT), when control of development shifts from maternal factors to the newly activated zygotic genome. Decades of studies in various model organisms suggest that the nucleocytoplasmic (N/C) ratio is a key regulator of zygotic genome activation (ZGA), though this relationship is more nuanced in some organisms than others. Changing the nuclear content, nucleus size or cell size has been shown to shift the timing of ZGA. Mechanistically, the N/C ratio is linked to fundamental cellular processes that regulate genome activities, including nuclear import, repressor titration, activator accumulation, cell cycle lengthening, and chromatin remodeling. In this review, we summarize the experimental evidence supporting the N/C ratio as a regulator of ZGA and describe the associated molecular mechanisms. We also discuss the limitations of the N/C ratio model, highlight species-specific differences, and examine outstanding questions.
Digital Object Identifier (DOI)
Publication Info
Published in Frontiers in Cell and Development Biology, Volume 14, 2026.
Rights
© 2026 Acker and Chen.
This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) license.. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
APA Citation
Acker, L., & Chen, H. (2026). Regulation of zygotic genome activation by the nucleocytoplasmic ratio. Frontiers in Cell and Developmental Biology, 14.https://doi.org/10.3389/fcell.2026.1819263