Transcription of MERVL retrotransposons is required for preimplantation embryo development

Akihiko Sakashita, Tomohiro Kitano, Hirotsugu Ishizu, Youjia Guo, Harumi Masuda, Masaru Ariura, Kensaku Murano, Haruhiko Siomi

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Zygotic genome activation (ZGA) is a critical postfertilization 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 two-cell stage during ZGA. Although MERVL expression is widely used as a marker of totipotency, the role of this retrotransposon in mouse embryogenesis remains elusive. Here, we show that full-length MERVL transcripts, but not encoded retroviral proteins, are essential for accurate regulation of the host transcriptome and chromatin state during preimplantation development. Both knockdown and CRISPRi-based repression of MERVL result in embryonic lethality due to defects in differentiation and genomic stability. Furthermore, transcriptome and epigenome analysis revealed that loss of MERVL transcripts led to retention of an accessible chromatin state at, and aberrant expression of, a subset of two-cell-specific genes. Taken together, our results suggest a model in which an endogenous retrovirus plays a key role in regulating host cell fate potential.

Original languageEnglish
Pages (from-to)484-495
Number of pages12
JournalNature genetics
Volume55
Issue number3
DOIs
Publication statusPublished - 2023 Mar

ASJC Scopus subject areas

  • Genetics

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