Replication-uncoupled MET1/DNMT1 activity shapes inheritance of DNA methylation.

Fiche publication

Date publication

juillet 2026

Journal

Cell reports

Auteurs

Membres identifiés du Cancéropôle Est :
Dr SELLES Benjamin

Tous les auteurs :
Edera A, Larue M, Leduque B, Michaud C, Selles B, Boutserin S, Biocanin I, Serret J, Leblanc O, Jullien P, Berger F, Barneche F, Sasaki T, Ingouff M, Quadrana L

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/42461724

Résumé

Cytosine methylation at CG sites is proposed to be maintained during DNA replication through a semiconservative mechanism. In mammals, this maintenance involves replication-coupled and replication-uncoupled steps; however, the underlying mechanisms and their possible conservation across eukaryotes remain unclear. Using live-cell sensors developed in this study to track CG methylation (mCG) dynamics, we uncovered that mCG maintenance extends far beyond DNA replication in the model plant Arabidopsis, with the major CG methyltransferase 1 (MET1) remaining associated with chromatin from S phase till G2 phase. Genetic dissection demonstrated that MET1, like its mammalian homolog DNA methyltransferase 1 (DNMT1), methylates nucleosome-associated DNA. Single-molecule duplex sequencing revealed that MET1/DNMT1-dependent methylation follows the rotational accessibility of nucleosomal DNA and is only partly templated by hemimethylated sites. This nucleosome-constrained de novo activity not only promotes mCG recovery after accidental loss but also shapes short- and long-term DNA methylation variation in plants and mammals.