The multi-loop aggregate/rosette chromatin architecture and functional dynamic organization of the human and mouse genome.

The dynamic three-dimensional chromatin architecture of genomes and the obvious co-evolutionary connection to its function – the storage and expression of genetic information – is still, after ~170 years of concentrated research, one of the central issues of our time. With a systems genomics combination of S2C and FCS together with analytical and simulated polymer models as well as scaling analysis it is now possible to gain insights into the architecture and dynamics with unprecedented detail. S2C is a novel superior selective high-throughput high-resolution chromosomal interaction capture of all physical genomic interactions (S2C) which has great advantages since it allows to reach an optimal combination of resolution, interaction frequency range, and multi-plexability, at unprecidented signal-to-noise ratio of multiple orders of magnitude. With a novel FCS approach it is possible to determine the relaxation of local concentration fluctuations of the chromatin fibre and derive based on an analytical polymer model the relation between average persistence length, mass density and chromatin architecture. Whereas S2C measures architectural parameters, the FCS approach allows to measure in vivo the dynamics of the architecture. As common ground polymer simulations using Monte Carlo and Brownian Dynamics approaches round-off both techniques in detail. In combination both approaches reach agreement concerning the 3D architecture and dynamics of genomes in detail as well as in the general scaling of genomes which yields the same scaling properties derived from the DNA base pair sequence organization itself. Consequently, this finally opens the path to detailed architectural and dynamic sequencing of genomes in a systems genomic manner which is of fundamental importance for genome understanding in perspective as far as diagnosis and treatment.