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Endogenous retrovirus-driven Pcgf5 plays critical roles in zygotic genome activation and noncanonical imprinting

Mashiko, S.; Yamamoto, T.; Minami, N.; Ikeda, S.; Honda, S.

2025-01-24 developmental biology
10.1101/2025.01.24.632300 bioRxiv
Show abstract

MERVL (murine endogenous retrovirus with leucine tRNA primer) is expressed during zygotic genome activation (ZGA) in mammalian embryos. Here, we show that the Polycomb group ring finger 5 (Pcgf5), a key component of Polycomb repressive complex 1 (PRC1), forms a chimeric transcript with MT2C_Mm, one of the long terminal repeat sequences of MERVL. Knockdown of Pcgf5 reduced developmental rates and decreased H3K27me3 and H2AK119ub1 modification during embryogenesis. In addition, not only genes expressed during ZGA but also imprinting genes were upregulated in Pcgf5 knockdown embryos. Moreover, Pcgf5 was involved in the addition of the H3K27me3 modification to the maternal Xist region. This is the first report of a MERVL-regulated transcript regulating Xist expression in mouse preimplantation embryos. Our results suggest that analysis of chimeric transcripts with MERVL will provide insight into the relationship between ZGA and noncanonical imprinting.

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