Compartmentalization of interphase chromosomes observed in simulation and experiment

Human interphase chromosomes were simulated as a flexible fiber with exclud ed volume interaction, which represents the chromatin fiber of each chromos ome. For the higher-order structures, we assumed a folding into 120 kb loop s and an arrangement of these loops into rosette-like subcompartments. Chro mosomes consist of subcompartments connected by small fragments of chromati n. Number and size of subcompartments correspond with chromosome bands in e arly prophase. We observed essentially separated chromosome arms in both ou r model calculations and confocal laser scanning microscopy, and measured t he same overlap in simulation and experiment. Overlap, number and size of c hromosome 15 subcompartments of our model chromosomes agree with subchromos omal foci composed of either early or late replicating chromatin, which wer e observed at all stages of the cell cycle and possibly provide a functiona lly relevant unit of chromosome territory compartmentalization. Computed di stances of chromosome specific markers both on Mb and 10-100 Mb scale agree with fluorescent in situ hybridization measurements under different prepar ation conditions. (C) 1999 Academic Press.