| Title |
Catalytic footprints of DNMT1 dynamics during mammalian cell state transitions |
| Authors |
Stankevičius, Vaidotas ; Kvederavičiūtė, Kotryna ; Gasiulė, Liepa ; Rukšėnaitė, Audronė ; Vilkaitis, Giedrius ; Klimašauskas, Saulius |
| DOI |
10.1016/j.celrep.2026.117435 |
| Full Text |
|
| Is Part of |
Cell reports.. Elsevier Inc.. 2026, vol. 45, iss. 6, art. no. 117435, p. 1-20.. ISSN 2639-1856. eISSN 2211-1247 |
| Keywords [eng] |
AdoMet cofactor analogs ; AdoMet-dependent methyltransferase ; bioorthogonal click labeling ; DNA cytosine-5 methylation ; Embryonic stem cells ; epigenetic reprograming ; Epigenomic tools ; precision genome editing |
| Abstract [eng] |
5-methylcytosine is a reversible regulatory mark in mammalian genomes whose distribution varies across genetic loci, cell types, and disease conditions. Cytosine-5 methylation is brought about by three AdoMet-dependent DNA methyltransferases (DNMTs) with primary tasks in de novo (DNMT3A and DNMT3B) or maintenance (DNMT1) methylation. However, the precise roles and interplay between the three methylation “writers” remain obscure. To selectively track an individual DNMT, we derived a heterozygous mESC line with chromosomal alleles expressing the wild-type and a sterically engineered variant of DNMT1. This enables catalysis-dependent chemical tagging DNMT1 methylation sites upon in-cell delivery of a synthetic AdoMet analog. Genome-wide mapping of the DNMT1 catalysome during naive-to-primed transition of mESC shows that DNMT1 contributes to de novo methylation of germline genes and competes with active demethylation at boundaries of CpG islands. Altogether, we provide a unique tool for chemical monitoring of individual methylation writers in minimally perturbed developmental and disease models. |
| Published |
Elsevier Inc |
| Type |
Journal article |
| Language |
English |
| Publication date |
2026 |
| CC license |
|
