Genomes are one of the major foundations of life due to their role in information storage, process regulation and
evolution. However, the sequential and three-dimensional structure of the human genome in the cell nucleus as
well as its interplay with and embedding into the cell and organism only arise scarcely. To achieve a deeper
understanding of the human genome the three-dimensional organization of the human cell nucleus, the
structural-, scaling- and dynamic properties of interphase chromosomes and cell nuclei were simulated and
combined with the analysis of long-range correlations in completely sequenced genomes as well as the
chromatin distribution in vivo. Using Monte Carlo and Brownian Dynamics methods, the 30 nm chromatin fibre
was simulated according to the Multi-Loop-Subcompartment (MLS) model, in which ~100 kbp loops form
rosettes, connected by a linker, and the Random-Walk/Giant-Loop (RW/GL) topology, in which 1-5 Mbp loops
are attached to a flexible backbone. Both the MLS and the RW/GL model form chromosome territories but only
the MLS rosettes result in distinct subcompartments visible with light microscopy and low overlap of
chromosomes, -arms and subcompartments. The MLS morphology, the size of subcompartments and chromatin
density distribution of simulated confocal (CLSM) images agree with the expression of fusionproteins from the
histones H1, H2A, H2B, H3, H4 and mH2A1.2 with the auto-fluorescent proteins CFP, GFP, YFP, DsRed-1 and
DsRed-2 which also revealed different interphase morphologies for different cell lines. Even small changes of
the model parameters induced significant rearrangements of the chromatin morphology. Thus, pathological
diagnoses, are closely related to structural changes on the chromatin level. The position of interphase
chromosomes depends on their metaphase location, and suggests a possible origin of current experimental
findings. The scaling behaviour of the chromatin fibre topology and morphology of CLSM stacks revealed finestructured
multi-scaling behaviour in agreement with the model prediction and correlations in the DNA
sequence. Review and comparison of experimental to simulated spatial distance measurements between genomic
markers as function of their genomic separation also favour an MLS model with loop and linker sizes of 63 to
126 kbp. Simulated and experimental DNA fragment distribution after ion-irradiation revealed also best
agreement with such an MLS. Correlation analyses of completely sequenced Archaea, Bacteria and Eukarya
chromosomes revealed fine-structured positive long-range correlation due to codon, nucleosomal or block
organization of the genomes, allowing classification as well as tree construction. This shows a complex
sequential organization of genomes closely connected to their three-dimensional organization. Visual inspection
of the morphology reveals also big spaces between the chromatin fibre allowing high accessibility to nearly
every spatial location, due to the chromatin occupancy <30% and a mean mesh spacing of 29 to 82 nm for nuclei
of 6 to 12 μm diameter. This agrees with a simulated displacement of 10 nm sized particles of ~1 to 2 μm takes
place within 10 ms, i.e. a moderately obstructed diffusion of biological molecules in agreement with
experiments. Thus, the local, global and dynamic characteristics of cell nuclei are not only tightly interconnected,
but also are integrated holisticly to fulfill the overall function of the genome
