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The zygotic genome of animal embryos is transcriptionally inactive upon fertilization,and becomes active after a certain period of development.As transcription can be controlled by the presence of 5-methylcytosines(5mC)in DNA,the global DNA methylation level in an embryo may play a role in the zygotic genome activation(ZGA).In mammals,the paternal genome is rapidly demethylated immediately after fertilization through 5mC hydroxymethylation,resulting in a decrease of the global DNA methylation level of the zygote genome.We found that the genome-wide erasure of DNA methylation upon fertilization in zebrafish embryos is not associated with 5mC hydroxymethylation.Instead,one of DNA glycosylases,hypothesized as XDG,appeared to mediate global DNA demethylation.xdg knockdown in zebrafish embryos causes an increase of the global DNA methylation level concomitantly with a reduction of the nuclear transcription level,ultimately resulting in embryonic lethality;conversely,xdg overexpression in embryos is sufficient to reduce the global DNA methylation level and induce earlier activation of zygotic genome transcription.Thus,XDG-mediated DNA demethylation through base excision and repairing is crucial for development of vertebrate embryos.