Transcription of MERVL retrotransposons is required for preimplantation embryo development.
Akihiko SakashitaTomohiro KitanoHirotsugu IshizuYoujia GuoHarumi MasudaMasaru AriuraKensaku MuranoHaruhiko SiomiPublished in: Nature genetics (2023)
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.
Keyphrases
- single cell
- genome wide
- rna seq
- gene expression
- poor prognosis
- transcription factor
- cell therapy
- dna methylation
- dna damage
- cell fate
- long non coding rna
- mass spectrometry
- copy number
- oxidative stress
- high resolution
- climate change
- mesenchymal stem cells
- genome wide identification
- pregnancy outcomes
- bone marrow
- data analysis