Three-Dimensional Organization of Chromosome Territories and the Human Cell Nucleus

Despite the successful linear sequencing of the human genome its three-dimensional structure is widely unknown. However, the regulation of genes — their transcription and replication — has been shown to be closely connected to the three-dimensional organization of the genome and the cell nucleus. On the bases of polymer physics we have recently developed detailed and quantitative structural models for the folding of the 30 nm chromatin fiber within the human interphase cell nucleus. A quantitative test of several plausible theories resulted in a best agreement between computer simulations of chromosomes, cell nuclei and experiments for the so called Multi-Loop-Subcompartment (MLS) model. Results concern the following properties: overlap of chromosome territories, -arms, -bands, 3D spatial distances between genomic markers as function of their genomic separation in base pairs, fractal analyis of simulations, mass distribution of chromatin in cell nuclei and the fragmentation distribution of cellular DNA after irradiation with carbon ions. Thus in an anology to the Bauhaus principle that “form follows function”, analyzing in which form DNA is organized might help us to understand genomic function.