Role of genome architecture in cell identity and in the response to perturbations

Role of genome architecture in cell identity and in the response to perturbations

Ferrari, Le Dily, Lioutas, Nacht, Quilez, Sharma, Vicent, Vidal, Wright

Progestin (Pg) addition to T47D breast cancer cells activates the Progesterone Receptor (PR) that binds to nucleosomaly organized promoter/enhancer regions of target genes along with kinases, histone modifying enzymes and chromatin remodeler, leading to coordinate activation or repression of genes clustered in topological associating domains (TADs) (Le Dily et al. Genes Dev 2014). In the context of the ERC Synergy Grant “4D Genome” and in collaboration with Thomas Graf, Marc Marti-Renom and Guillaume Filion and the 4D Genome Unit (François Le Dily, Enrique Vidal) we continue exploring the relevance of genome architecture for cell identity, the response to perturbations – such as inhibition of transcription, energy supply or signalling - and the epigenetic memory of various normal and cancer cells. We have generated a catalog of lncRNAs expressed in the breast cancer cell line T47D and have identified a few that change expression in response to hormone. We want to explore their potential contribution to genome architecture using CRISPR-cas9 approaches.