Maria Pia Cosma
Centre for Genomic Regulation (CRG), Barcelona, 08003, Spain.
Dissecting the 3D-chromatin organization in cell physiology is a key area of investigation. By using quantitative super-resolution nanoscopy, we identified a novel chromatin fiber assembly and its relation with naïve pluripotency. Nucleosomes are arranged in groups of various sizes, the nucleosome clutches, which control gene function. We recently visualized the structure of cohesin-mediated loops in human cells and discovered that transcriptional-dependent supercoiling controls loop formation and 3D-genome organization. Furthermore, by combining imaging and genomic approaches, we designed MiOS, a powerful integrated strategy to model the folding of key pluripotency genes at nucleosome resolution. Overall, super-resolution microscopy combined with genomic and modeling methods allowed us to dissect the functional role of transcription-mediated supercoiling and the nucleosome level structure of genes, which ultimately are key features controlling gene activity.