Single-cell temporal tracking of epigenetic DNA marks

Informations projet

EpiTrack

N° de convention de subvention: 742654

DOI

10.3030/742654

Projet clôturé

Date de signature de la CE 21 Avril 2017

Date de début 1 Septembre 2017

Date de fin 28 Février 2023

Financé au titre de

• EXCELLENT SCIENCE - European Research Council (ERC)

Coût total

€ 2 499 875,00

Contribution de l’UE

€ 2 499 875,00

Coordonné par

VILNIAUS UNIVERSITETAS
Lithuania

Periodic Reporting for period 4 - EpiTrack (Single-cell temporal tracking of epigenetic DNA marks)

Période du rapport: 2022-03-01 au 2023-02-28

Résumé du contexte et des objectifs généraux du projet

Epigenetics, the study of the changes in organisms caused by modification of gene expression rather than alteration of the genetic code itself, has taken centre stage in our understanding of gene regulation, cellular differentiation and human disease. The process of adding a methyl group to a DNA molecule (DNA methylation) is one of the most prevalent epigenetic modifications in mammals whereby three major DNA methylation enzymes (DNMT1, DNMT3a and DNMT3b) deposit tens of millions of these "diacritic marks" in the genome creating cell type-specific methylation patterns. Although DNA methylation has been extensively investigated, key mechanisms of these fascinating events remain obscure. The project aims to engineer an advanced cellular system (named liveTAG) that will give a comprehensive view of the roles that the three DNA methyltransferases play in establishing cell-specific genomic methylation patterns and how they govern cell variability and ability to differentiate during mammalian development. The study aims to deepen our understanding of epigenetic regulation in mammalian cells which has important implications in human development and disease.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

Using CRISPR-CAS genome editing technology and new knowledge gained during the project we have successfully redesigned the DNMT1 methylase inside mouse cells for selective deposition of trackable chemical entities in DNA. In parallel, we have advanced our development of high resolution analytical tools for mapping the deposited chemical entities on the genome scale in single cells.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

The developed unique tools pave the way to selective chemical tracking of key epigenetic events underlying reprogramming of stem cells to other cell types during mammalian differentiation. These studies will provide new insights into the epigenetic regulation in mammalian cells which has important implications for our understanding human development and disease.

Strategy for small molecule-dependent chemical tagging of cognate methylation sites (liveTAG)