On the detailed 3D multi-loop aggregate/rosette chromatin architecture and functional dynamic organization of the human and mouse genome.

Although the sequence of the human genome is known, the relation of its three-dimensional dynamic architecture with its function – the storage and expression of genetic information – remains one of the central unresolved issues of our time. Here we show how simulations of the structural-, scaling- and dynamic properties of interphase chromosomes and cell nuclei with Monte Carlo and Brownian Dynamics methods (WP4) can be combined with experimental structure preserving 3D FISH combined with high-resolution fluorescence microscopy that allows determination of the centre of mass of target fluorophors at a resolution of ~30 nm – beyond the classical resolution limit (WP2), in vivo chromatin labelling (WP2) as well as our newly developed combination of chromosome conformation capture technology and high-throughput deep sequencing (WP2). Best agreement is reached both for the Prader-Willi/Angelmann region and the Immunoglobin heavy-chain (Igh) locus for a Multi-Loop-Subcompartment (MLS) model of chromosome organization predicting 60-150 kbp loop aggregates separated by a similar linker. Beyond, DNA sequence correlation analysis of completely sequenced genomes reveals fine structured multi-scaling long-range correlations. The fine structure in the human case is attributable to nucleosome positioning (WP1) and transcription (WP3). In summary, genomes show a complex sequential and three-dimensional organization related closely to each other in a system biological/medical co-evolutionarily developed entity.