Mechanisms of TET2 DNA demethylase recruitment to specific genomic regions

Informacje na temat projektu

TET2rec

Identyfikator umowy o grant: 796341

DOI

10.3030/796341

Projekt został zamknięty

Data podpisania przez KE 20 Lutego 2018

Data rozpoczęcia 1 Marca 2018

Data zakończenia 29 Lutego 2020

Finansowanie w ramach

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Koszt całkowity

€ 200 194,80

Wkład UE

€ 200 194,80

Koordynowany przez

KOBENHAVNS UNIVERSITET
Denmark

Periodic Reporting for period 1 - TET2rec (Mechanisms of TET2 DNA demethylase recruitment to specific genomic regions)

Okres sprawozdawczy: 2018-03-01 do 2020-02-29

Podsumowanie kontekstu i ogólnych celów projektu

Acute myeloid leukemia (AML) patients frequently harbor mutations in the epigenetic modifier TET2, which is a DNA demethylase. DNA methylation is an epigenetic modification that occurs predominantly at CpG dinucleotides and have a major impact on transcription. Accordingly, it plays key roles in cellular identity specification, and, when deregulated, in cancer. The importance of DNA methylation in cancer is underscored by the clinical use of hypomethylating agents in the treatment of AML and other myeloid disorders. DNA methylation is a reversible process and, only recently, it was discovered that TET (Ten-eleven Translocation) proteins mediate DNA demethylation. Jawed vertebrates have three TET homologues (TET1, TET2 and TET3). All TET proteins contain a C-terminal catalytic region. Remarkably, while TET1 and TET3 share an N-terminal DNA binding domain (CXXC motif), TET2 has lost its CXXC motif during evolution. Therefore, it is not understood how TET2 binds DNA. The main goal of this project is to understand how TET2 binds to specific regions of the genome.

Prace wykonane od początku projektu do końca okresu sprawozdawczego oraz najważniejsze dotychczasowe rezultaty

We have investigated the mechanisms of TET2 recruitment to DNA using different approaches including chromatin immunoprecipitation, RNA-sequencing and mass spectrometry. The hits identified hold great potential as TET2 interactors for future research. They can be used by scientists in academia to further elucidate the mechanism of TET2 function in health and disease.

Innowacyjność oraz oczekiwany potencjalny wpływ (w tym dotychczasowe znaczenie społeczno-gospodarcze i szersze implikacje społeczne projektu)

Furthermore, the main researcher has acquired a deep knowledge of the hematology and epigenetics fields and expertise in a wide range of techniques. She has also improved her communication, teaching and science dissemination skills. Altogether, she has become a more mature and competitive scientist with an extended network of collaborators.

Tet2rec