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. Overall design: For the SLAM-seq profiling of mouse preimplantation embryos from nine stages, we adopted the criteria of 2 mM 4SU, 6-hour interval labeling and 10 embryos per sample for profiling; For the ATAC-seq, we selected the embryos from seven stages across the preimplantation development; For the function validation of KLF17, we collected contrl (ctrl), KO, mKO, pKO embryos at the M2C stage to perform SLAM-seq.