Repeat elements activating lncRNAs drives zygotic genome activation

Vertebrate life begins with fertilization, then the zygote genome is activated after transient silencing, termed zygotic genome activation (ZGA). The mechanism of how ZGA initiates is far from clear although it underlay the mystery of totipotency and start of life. The specific property of the minor ZGA implied the possible critical role of ncRNA in the initiation of ZGA. Here we delineated the expression profile of the lncRNAs in the mouse early embryo development and elucidated their critical role in the minor ZGA. LncRNAs showed closer correlation with minor ZGA, they activated earlier than the protein coding genes (PCGs) and suppressed quickly after ZGA. H3K9me3 enrichment prior the ZGA could explain the suspended expression of major ZGA PCGs albeit they possess the PolII pre-configuration. The PolII enriched MuERV-L was found around the TSS of the minor ZGA lncRNAs, and they were responsible for the activation of the minor ZGA lncRNAs and the subsequent embryo development. Our work suggested the MuERV-L mediated minor ZGA lncRNA activation as a critical driver between the epigenetic reprogramming triggered by fertilization and the embryo developmental program, thus provided clues for understanding totipotency and starting of life. Total RNA profiles of mouse early embryonic samples were generated by deep sequencing.