The mechanisms beyond chromosome folding within the nuclei of eukaryotic cells have fundamental implications in important processes like gene expression and regulation. Yet, they remain widely unknown. Unveiling the secrets of nuclear processes requires a cross-disciplinary approach combining experimental techniques to theoretical, mathematical and physical modeling. In this review, we discuss our current understanding of the generic aspects of genome organization during interphase in terms of the conceptual connection between the large-scale structure of chromosomes and the physics beyond the crumpled structure of entangled ring polymers in solution. Then, we employ this framework to discuss recent experimental and theoretical results for microrheology of Brownian nanoprobes dispersed in the nuclear medium.
