Orateur
Description
Marco Di Stefano, Ivana Jerkovic, Giacomo Cavalli
Institute of Human Genetics, Université de Montpellier, CNRS, Laboratoire de Chromatine et Biologie Cellulaire, 34094 Montpellier, France
Chromosome structural organization contributes to fundamental processes in the cell nucleus, including DNA transcription, replication, and repair. Experimental and theoretical works unveiled that chromosome spatial organization is a complex aggregate of layers: entire chromosomes occupy distinct volumes of the nucleus, called territories; regions of tens of Mega-bases (Mb) tend to organize in active and repressed (A/B) compartments; regions up to one Mb organize in domains (TADs); and loops may bring in contacts gene promoters with enhancers. However, the forces regulating these layers and their interplay with transcription activity are still elusive. Here, I will present an approach to studying these organizing principles in the genomic region around the Zfp608 gene in mouse Embryonic stem cells, where the gene is transcriptionally inactive, and in neural progenitor cells (NPC), where it is active. By applying biophysical structural modeling, we focus on epigenomic-driven interactions between chromatin of the same type (e.g., active chromatin attracts other regions with the same chromatin marks), loop-extrusion dynamics, and the effect of promoter-enhancer interactions. Extensive quantitative analysis and comparison with Capture Hi-C data drives the models’ parameterization. This project aims to show that biophysical models can help explain how experimentally observed structures are formed and unravel potential factors and molecular mechanisms regulating chromosome organization in different cell types.
