Fine-tuning of gene expression through the Mettl3-Mettl14-Dnmt1 axis controls ESC differentiation Journal Article
| Authors: | Quarto, G.; Li Greci, A.; Bizet, M.; Penning, A.; Primac, I.; Murisier, F.; Garcia-Martinez, L.; Borges, R. L.; Gao, Q.; Cingaram, P. K. R.; Calonne, E.; Hassabi, B.; Hubert, C.; Herpoel, A.; Putmans, P.; Mies, F.; Martin, J.; Van der Linden, L.; Dube, G.; Kumar, P.; Soin, R.; Kumar, A.; Misra, A.; Lan, J.; Paque, M.; Gupta, Y. K.; Blomme, A.; Close, P.; Estève, P. O.; Caine, E. A.; Riching, K. M.; Gueydan, C.; Daniels, D. L.; Pradhan, S.; Shiekhattar, R.; David, Y.; Morey, L.; Jeschke, J.; Deplus, R.; Collignon, E.; Fuks, F. |
| Article Title: | 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 upregulation of key differentiation genes during early differentiation depends on the dynamic balance between increased 5mC and decreased m6A. Our findings add a surprising dimension to our understanding of how epigenetics and epitranscriptomics combine to regulate gene expression and impact development and likely other biological processes. © 2024 Elsevier Inc. |
| Keywords: | controlled study; protein expression; human cell; nonhuman; animal cell; mouse; gene expression; embryonic stem cell; cell differentiation; immunofluorescence; dna methylation; protein purification; epigenetics; histone; chromatin immunoprecipitation; western blotting; immunoprecipitation; dna methyltransferase; dna extraction; bioluminescence; rna extraction; differentiation; diagnostic test accuracy study; principal component analysis; gene ontology; size exclusion chromatography; dnmt1; escs; human; article; hek293 cell line; hela cell line; real time reverse transcription polymerase chain reaction; mettl3; epitranscriptomics; m<sup>6</sup>a; mettl14 |
| Journal Title: | Cell |
| Volume: | 188 |
| Issue: | 4 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2025-02-20 |
| Start Page: | 998 |
| End Page: | 1018.e26 |
| Language: | English |
| DOI: | 10.1016/j.cell.2024.12.009 |
| PUBMED: | 39826545 |
| PROVIDER: | scopus |
| PMCID: | PMC12160003 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
