Mouse embryos do not wait for the MBT: chromatin and RNA polymerase remodeling in genome activation at the onset of development.

In Xenopus and Drosophila embryos, activation of the zygotic genome occurs after a series of rapid nuclear divisions in which DNA replication occupies most of the cell cycle. In these organisms, it has been proposed that zygotic transcription does not begin until a threshold nucleocytoplasmic ratio has been obtained in which repressive factors are titrated out and interphase becomes long enough to allow synthesis of transcripts. In mammalian embryos, however, a model of threshold nucleocytoplasmic ratios does not seem to apply, as beginning with the 1-cell stage, there are regulated cell cycles with the expression of zygotic transcripts during the cleavage period. By taking advantage of the slower kinetics at the onset of mouse development, we have characterized changes in chromatin structure and the basal transcription machinery throughout the transition from transcriptional incompetence, to minor activation of the zygotic genome during the 1-cell stage, and through major genome activation at the 2-cell stage. Further maturation of chromatin structure continues through subsequent cleavage cycles as a foundation for the first cellular differentiations in the blastocyst. The epigenetic chromatin modifications that occur during the cleavage period may have long range and inheritable effects and are undoubtedly important in the ability of the mammalian oocyte to remodel previously defined nuclear structures and cell fates.