Nascent transcript sequencing visualizes mouse preimplantation embryonic genome activation

Embryonic genome activation (EGA), a pivotal transcriptional event during preimplantation development, is accompanied by post-transcriptional regulation of maternal mRNAs. Disentangling the transcriptional output of the newly activated embryonic genome from concomitant post-transcriptional processing is important for decoding EGA dynamics.Here, using optimized low-input SLAM-seq (thiol(SH)-linked alkylation for the metabolic sequencing) in mouse embryos, we delineates the temporal hierarchy of EGA nascent transcription during mouse preimplantation embryogenesis and uncovers a mechanistic link between EGA and the first lineage specification, providing new insights into the regulatory architecture of early mammalian development.