A program of successive gene expression in mouse one-cell embryos

At the moment of union in fertilization, sperm and oocyte are transcriptionally silent. The ensuing onset of embryonic transcription (embryonic genome activation, EGA) is critical for development, yet its timing and profile are unknown in any vertebrate species. We here dissect hitherto inaccessible transcription during EGA by high resolution single-cell RNA-sequencing of precisely synchronized mouse one-cell embryos. This reveals a program of embryonic gene expression (immediate EGA, iEGA) initiating within four hours of fertilization. Expression during iEGA produces canonically-spliced transcripts, occurs substantially from the maternal genome, and is mostly down-regulated at the two-cell stage. Transcribed genes predict regulation by transcription factors (TFs) associated with cancer, including c-Myc. Blocking c- Myc or other predicted regulatory TF activities disrupts iEGA and induces acute developmental arrest. These findings illuminate intracellular mechanisms that regulate the onset of mammalian development and promise a new paradigm for the study of cancer RNASeq comparison of 10058-F4/alpha-amanitin treated versus control untreated one-cell embryo