摘要：SummaryZFP57 and ZFP445 maintain genomic imprinting in mouse embryos. We found DNA methylation was lost at most examined imprinting control regions (ICRs) in mouseZfp57mutant ES cells, which could not be prevented by the elimination of three TET proteins. To elucidate methylation maintenance mechanisms, we generated mutant ES clones lacking three major DNA methyltransferases (DNMTs). Intriguingly, DNMT3A and DNMT3B were essential for DNA methylation at a subset of ICRs in mouse ES cells although DNMT1 maintained DNA methylation at most known ICRs. These were similarly observed after extended culture. Germline-derived DNA methylation was lost at the examined ICRs lacking DNMTs according to allelic analysis. Similar to DNMT1, DNMT3A and DNMT3B were required for maintaining DNA methylation at repeats, genic regions, and other genomic sequences. Therefore, three DNA methyltransferases play complementary roles in maintaining DNA methylation in mouse ES cells including DNA methylation at the ICRs primarily mediated through the ZFP57-dependent pathway.Graphical abstractDisplay OmittedHighlights•ZFP57 maintains DNA methylation at the ICR of most imprinted regions in ES cells•TET proteins may not be essential for maintaining most ICR DNA methylation in ES cells•DNMT3 is required for the maintenance of DNA methylation at a subset of ICRs in ES cells•Maintenance functions of DNMT1 and DNMT3 are complementary at repeats and genic regionsBiological sciences; Molecular biology; Cell biology; Stem cell research;, Genetics; Epigenetics
