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

textabstractTo study the three-dimensional organization of chromosome territories and the human interphase cell nucleus we developed models which could be compared to experiments. Despite the successful linear sequencing of the human genome its 3D-organization is widely unknown. Using Monte Carlo and Brownian dynamics simulations we managed to model the chromatin fiber as a wormlike-chain polymer. A typical chromosome consists of 20.000 and a nucleus with all 46 chromosomes of 1.200.000 polymer chain segments. The parallel simulations are performed on a SP2512 and a Cray T3E. With fluorescent in situ hybridization and confocal microscopy we determined genomic marker distributions and chromosome arm overlap. Best agreement between simulations and experiments is reached for a Multi-Loop-Subcompartment model (126 kbp loops connected to rosettes connected by a 126 kbp chromatin linker). A fractal analysis of simulations leads to multi-fractal behaveour in good agreement with porous network research. The formation of chromosome territories was shown as predicted and low overlap of chromosomes and their arms was also reached in contrast to other models. Thus, the human interphase cell nucleus shows a higher degree of determinism than previously thought