Reflections on the organization and the physical state of chromatin in eukaryotic cells

In recent years, our perception of chromatin structure and organization in the cell nucleus has changed in fundamental ways. The 30 nm chromatin fiber has lost its status as an essential in vivo structure. Hi-C and related biochemical methods, advanced electron and super-resolved fluorescence microscopy, together with concepts from soft matter physics, have revolutionized the field. A comprehensive understanding of the structural and functional interactions that regulate cell cycle and cell type specific nuclear functions appears within reach, but it requires the integration of top-down and bottom-up approachs. In this review, I present an update on nuclear architecture studies with an emphasis on organization and the controversy regarding the physical state of chromatin in cells.