Institut de recherche biomédicale
     
    Vous êtes ici : Accueil / La Recherche / Développement, Reproduction, Cancer / Equipe J. Chaumeil

    Epigénétique et organisation nucléaire dans la recombinaison et le développement

    •  

    Responsable :

    The general aim of the team is to investigate the functional role of 3D genome conformation, chromatin and nuclear organization in the regulation of gene regulation and V(D)J recombination during hematopoiesis and malignant transformation as well as in immune-related diseases.

     

    Objectives

    Modulation of chromatin environments, non-coding RNAs, 3D genome conformation and nuclear organization is tightly linked to the establishment and/or maintenance of cell-type specific transcription profiles during development and homeostasis, as well as the regulation of nuclear functions like DNA recombination and repair. Furthermore, it is becoming increasingly clear that alterations in these epigenomic features are linked to numerous diseases, in particular cancer. However, the functional relationships between epigenomic mechanisms, cell differentiation, DNA recombination and malignant transformation remain unclear. Hematopoiesis represents a remarkable model to explore these questions. Indeed, it represents a key-differentiation program as it allows the daily release of billions of blood cells, from red blood cells to platelets, macrophages and lymphocytes. Moreover, during lymphocyte differentiation, V(D)J recombination is the key-process by which the virtually infinite diversity of antigen receptors is created to combat the equally vast array of antigens. As these processes of differentiation and programmed rounds of DNA cleavage and joining occur every day in millions of cells, even a tiny error rate can lead to genome misregulation and/or genome instability underlying oncogenic transformation (leukemia/lymphomas) and immune-related diseases. Although epigenomic features have been correlated with the regulation of these programs, their functional role and the consequences of their alterations in the origins of diseases are still largely unknown. The project of the team is to explore these key questions This should provide important insights into the role of genome and nuclear dynamics in gene regulation and the preservation of genome and cell integrity.

    A state-of-the-art combination of single cell analyses and genome-wide approaches are used to investigate:

    (1) the functional impact of chromatin and nuclear environment on antigen receptor loci expression and recombination,

    (2) the links between 3D locus conformation, cis/trans genomic interactions, and regulation of recombination,

    (3) the role of chromosome conformation and nuclear organization in hematopoiesis, oncogenic transformation, and immune-related diseases.

    This should provide new insights into the role of chromatin and nuclear dynamics in the regulation of gene expression, DNA recombination, preservation of genome integrity and the origins of lymphoid-related diseases.

     

    Team's news

     

    • Laureate of the ATIP-Avenir junior group leader program 2015
    • Official Lab opening: Spring 2016.

     

    Financial supports