Fine-tuning of gene expression through the Mettl3-Mettl14-Dnmt1 axis controls ESC differentiation.

ABSTRACT: The marking of DNA, histones, and RNA is central to gene expression regulation in development and disease. Recent evidence links N6-methyladenosine (m⁶A), installed on RNA by the METTL3-METTL14 methyltransferase complex, to histone modifications, but the link between m⁶A and DNA methylation remains scarcely explored. This study shows that METTL3-METTL14 recruits the DNA methyltransferase DNMT1 to chromatin for gene-body methylation. We identify a set of genes whose expression is fine-tuned by both gene-body 5mC, which promotes transcription, and m⁶A, which destabilizes transcripts. We demonstrate that METTL3-METTL14-dependent 5mC and m⁶A are both essential for the differentiation of embryonic stem cells into embryoid bodies and that the upregulat

SUBMITTER: Quarto G 

PROVIDER: S-EPMC12160003 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature