Genome stability during development depends on the precise transmission of genetic and epigenetic information in cells. DNA methylation is a critical mechanism that prevents genome instability. In rapid-developing organisms such as zebrafish, this process is even more important, as post-replication methylation ensures the preservation of parental methylation patterns after mitosis. A study in Communications Biology shows that the relationship between DNA replication and methylation is antagonistic and needs a careful balance to ensure normal development in zebrafish larvae. The researchers generated zebrafish with a mutant allele for dnmt1, a gene previously identified as being critical for development and maintaining global CG methylation levels; dnmt1 zebrafish mutants were viable and showed genome-wide DNA hypomethylation. By contrast, mutants for pole1, encoding the catalytic subunit of DNA polymerase epsilon, showed increased methylation levels. When a double dnmt1/pole1 mutant was produced, methylation levels were restored, showing the antagonistic effect of both genes. These results contribute to a better understanding of genome regulation during stages of rapid cell division and early developmental stages.
Original reference: Lawir, D.F. et al. Commun. Biol. 7, 31 (2024)
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