Plasticité de l'épigénome: mécanismes et physiopathologie – EpiGO

Changes in the epigenomic state and nuclear organization of eukaryotic cells are important driving forces for proper regulation of gene expression in response to developmental and environmental signals. To gain further insight into how these - usually heritable, yet reversible - modifications influence gene expression programs and ultimately cell fate, the project will be focused on two families of chromatin modulators playing key roles in transcription: the TIF1 (Transcriptional Intermediary Factor 1) and HP1 (Heterochromatin protein 1) gene products. Through a combination of genetic, biochemical, and genomic approaches, we will determine (i) the epigenetic mechanisms by which TIF1' represses liver-specific expression programs for the proper control of quiescence and how defects in these mechanisms lead to oncogenesis, (ii) the precise mechanisms by which cell differentiation induces heterochromatin targeting of TIF1' and which developmental functions of TIF1' require association with HP1, and (iv) the exact roles the three HP1 variants exert in the mouse as modulators of chromatin dynamics. The final outcome resulting from these studies will certainly provide insights into the epigenetic mechanisms that control mammalian development, tissue homeostasis and malignancy.