The RNA m⁶A landscape of mouse oocytes and preimplantation embryos

Despite the significance of N⁶-methyladenosine (m⁶A) in gene regulation, the requirement for large amounts of RNA has hindered m⁶A profiling in mammalian early embryos. Here we apply low-input methyl RNA immunoprecipitation and sequencing to map m⁶A in mouse oocytes and preimplantation embryos. We define the landscape of m⁶A during the maternal-to-zygotic transition, including stage-specifically expressed transcription factors essential for cell fate determination. Both the maternally inherited transcripts to be degraded post fertilization and the zygotically activated genes during zygotic genome activation are widely marked by m⁶A. In contrast to m⁶A-marked zygotic ally-activated genes, m⁶A-marked maternally inherited transcripts have a higher tendency to be targeted by microRNAs. Moreover, RNAs derived from retrotransposons, such as MTA that is maternally expressed and MERVL that is transcriptionally activated at the two-cell stage, are largely marked by m⁶A. Our results provide a foundation for future studies exploring the regulatory roles of m⁶A in mammalian early embryonic development.