Preventing CpG hypermethylation in oocytes safeguards mouse development.

ABSTRACT: Except for regulatory CpG-island sequences, genomes of most mammalian cells are widely DNA-methylated. In oocytes, though, DNA methylation (DNAme) is largely confined to transcribed regions. The mechanisms restricting de novo DNAme in oocytes and their relevance thereof for zygotic genome activation and embryonic development are largely unknown. Here we show that KDM2A and KDM2B, two histone demethylases, prevent genome-wide accumulation of histone H3 lysine 36 di-methylation, thereby impeding DNMT3A-catalyzed DNAme. We demonstrate that aberrant DNAme at CpG islands inherited from Kdm2a/Kdm2b double-mutant oocytes represses gene transcription in two-cell embryos. Aberrant maternal DNAme impairs pre-implantation embryonic development, which is suppressed by Dnmt3a deficiency during oogenesi

SUBMITTER: Kawamura YK 

PROVIDER: S-EPMC12687725 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature