Periodic Reporting for period 4 - 4D-GenEx (Spatio-temporal Organization and Expression of the Genome)
Período documentado: 2022-10-01 hasta 2024-03-31
Thanks to the recent technological progress, we know that 3D genome conformation plays the key role in gene expression. In particular, we know that certain genes are often found in proximity in 3D space inside the nucleus. Also, the spatial folding of the genome allows certain genomic regions called ‘enhancers’ to influence the decision whether to express a gene or not. There are many examples where it is directly the perturbation of 3D genome folding that activates oncogenes, especially in many carcinomas. Despite those observations, our understanding of the mechanisms at play, in healthy and pathological contexts, is still limited.
Using breast cancer cells, we study distinct sets of genes that are sensitive to the hormone estrogen. Using cutting-edge microscopy, we observe the 3D positions and activity (expressed or not) of each of these genes. We combine this approach technologies, such as CRISPR and others, to perturb different factors (mutations, inactivation of enhancers) as to understand the fundamental mechanisms governing the decisions to express genes or not.