Mouse fertilization triggers a conserved transcription program in one-cell embryos

Following fertilization, the new embryo reprograms parental genomes to begin transcription (embryonic genome activation, EGA). EGA is indispensable for development, but its dynamics, profile or when it initiates in vertebrates are unknown. We here characterize the onset of transcription in mouse one-cell embryos. Precise embryo staging eliminated noise to reveal a cascading program of de novo transcription initiating within six hours of fertilization. This immediate EGA (iEGA) utilized canonical promoters, produced spliced transcripts, was distinctive and predominantly driven by the maternal genome. Expression represented pathways not only associated with embryo development but with cancer. In human one-cell embryos, hundreds of genes were up-regulated days earlier than thought, with conservation to mouse iEGA. These findings provide a functional basis for epigenetic analysis in early-stage embryos and illuminate networks governing totipotency and other cell-fate transitions. One Sentence SummaryFertilization instates transcription in mouse and human one-cell embryos far sooner than thought and is programmed.