Molecular mechanisms of maintenance DNA methylation

Maintenance DNA methylation is essential for the stable inheritance of epigenetic information in vertebrates. While DNMT1 has long been recognized as the principal maintenance methyltransferase, recent studies have shown that its activity critically depends on ubiquitin signaling. Specifically, the...

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Published inGenes & Genetic Systems p. 25-00073
Main Authors Mulholland, Christopher B., Nishiyama, Atsuya
Format Journal Article
LanguageEnglish
Published Japan The Genetics Society of Japan 2025
Subjects
CDCA7
DNMT1
HELLS/LSH
maintenance of DNA methylation
ubiquitin
UHRF
UHRF
CDCA7
DNMT1
HELLS/LSH
ubiquitin
maintenance of DNA methylation
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Summary:Maintenance DNA methylation is essential for the stable inheritance of epigenetic information in vertebrates. While DNMT1 has long been recognized as the principal maintenance methyltransferase, recent studies have shown that its activity critically depends on ubiquitin signaling. Specifically, the E3 ligase UHRF1 enables DNMT1 recruitment and activation at hemimethylated sites through dual monoubiquitylation of both replication-associated and histone substrates. These insights have revised classical models of maintenance methylation and revealed new layers of regulation involving chromatin context, histone modifications, and nucleosome remodeling. In this review, we summarize the current understanding of the molecular mechanisms underlying DNMT1-mediated maintenance methylation, with a particular focus on ubiquitin-dependent pathways and their interplay with chromatin architecture.
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ISSN:1341-7568
1880-5779
1880-5779
DOI:10.1266/ggs.25-00073