New modes of action of the TET epigenetic proteins        

Abstract : DNA methylation is the best-characterized epigenetic modification and has been involved in a large number of biological processes. Despite its role in long-term silencing, DNA methylation is more dynamic than originally thought as active DNA demethylation has also been observed. Recently, a new field in epigenetic regulation has emerged with the identification of 5-hydroxymethylcytosine (5hmC), which consists in an intermediate of DNA demethylation. This breakthrough discovery of 5hmC, dubbed “the sixth base” of the genome, sparked intense efforts to characterize its specialized enzymatic machinery, composed of three proteins of the Ten-Eleven Translocation family (TET1, TET2 and TET3). The present PhD project aims to decipher the molecular mechanisms of TET-mediated gene expression regulation, for which very little is known. Various biochemical approaches and genome-wide location analysis (ChIP-Seq) will be performed both in cell lines and in a physiologically relevant mouse model system. The proposed project is in line with the current international key challenges in the epigenetic field and it will contribute to make a significant impact on understanding TET proteins function, and will further assess the role of 5hmC in epigenetic regulation. Further insight into how DNA methylation is dynamically regulated will broaden our vision of the epigenetic plasticity of the genome, with important implications in key biological processes as well as in human diseases
Promoteur/Supervisor : Prof. Fuks François
Email :
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Centre de recherche/Research center : Laboratory of Cancer Epigenetics
Faculté/Faculty : Faculty of Medicine/Faculté de Médecine
Ecole doctorale/Graduate Colleges : Biomedical and Pharmaceutical Science/Sciences biomédicales et pharmaceutiques
Ecole doctorale thématique/Graduate School (French Only): Biologie Cellulaire et Moléculaire, Biochimie (BCMB)

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