Dynamic self-organization of the human genome during the cell cycle

The hierarchical organization of the chromatin fiber, the functional form of DNA in cells, has been extensively studied from a single nucleosome to the genome-wide scale. Chromosome conformation capture techniques revealed a detailed static picture of the genome's 3D folded state inside the cell nucleus, revealing presence of loops, topologically associating domains, A/B compartments and chromosome territories [1]. In addition, chromatin organization was found to resemble a fractal globule inside the nucleus [2]. However, chromatin organization is not static but dynamically changes throughout the lifetime of a cell [3]—how it changes during the cell cycle remains an open question. In this work, we study the 3D chromatin organization inside the human cell nucleus and the changes of this organization during the cell cycle. By combining small angle X-ray scattering and high-resolution light microscopy, we investigate chromatin organization across a wide range of length scales during the cell cycle. In addition, we employed targeted biochemical perturbations to identify active cellular processes contributing to chromatin organization at these distinct length scales. Taken together, our data reveal that the 3D chromatin organization changes during the cell cycle in a length scale dependent manner [4]. This research was supported by the National Institutes of Health Grant R01-GM145924 and by the National Science Foundation Grants CAREER PHY-155488, CMMI-1762506 and PHY-2210541.