Transcription of Murine Endogenous Retrovirus MERVL Is Required for Progression of Development in Early Preimplantation Embryos

Zygotic genome activation (ZGA) is a critical post-fertilization step that promotes totipotency and allows different cell fates to emerge in the developing embryo. MERVL, murine endogenous retrovirus-L, is transiently upregulated at the 2-cell stage around the time of ZGA. Although MERVL expression is widely used as a marker of totipotency, the role of this retrotransposon in mouse embryogenesis remains elusive. Here, we develop a method for consistent knockdown of interspersed copies of MERVL and show that MERVL RNA, but not encoded retroviral proteins and their long terminal repeat (LTR) promoter, is essential for accurate regulation of the host transcriptome and chromatin state during preimplantation development. MERVL knockdown (KD) results in embryonic lethality due to defects in differentiation and genomic stability. Furthermore, transcriptome and epigenome analysis revealed that MERVL-KD embryos retained an accessible chromatin state at, and aberrant expression of, a subset of 2-cell specific genes at mid-preimplantation stages. Taken together, our results suggest a model in which an endogenous retrovirus plays a critical role in regulating host cell fate potential.