Single-cell temporal tracking of epigenetic DNA marks

Informazioni relative al progetto

EpiTrack

ID dell’accordo di sovvenzione: 742654

DOI

10.3030/742654

Progetto chiuso

Data della firma CE 21 Aprile 2017

Data di avvio 1 Settembre 2017

Data di completamento 28 Febbraio 2023

Finanziato da

• EXCELLENT SCIENCE - European Research Council (ERC)

Costo totale

€ 2 499 875,00

Contributo UE

€ 2 499 875,00

Coordinato da

VILNIAUS UNIVERSITETAS
Lithuania

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

Periodo di rendicontazione: 2022-03-01 al 2023-02-28

Sintesi del contesto e degli obiettivi generali del progetto

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.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

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.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

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)