%0 Generic
%A Bohn, Manfred
%D 2010
%F heidok:10601
%K chromatin folding , polymer models , biophysics
%R 10.11588/heidok.00010601
%T Modelling of Interphase Chromosomes : From Genome Function to Spatial Organization
%U https://archiv.ub.uni-heidelberg.de/volltextserver/10601/
%X Genome function in higher eukaryotes involves major changes in the spatial organization of the chromatin fiber. Nevertheless, our understanding  of chromatin folding is remarkably limited. Experimental results suggest that chromatin loops not only impact transcriptional regulation but also act as a major epigenetic mechanism, playing a pivotal role in the observed compartmentalization of chromosomes. However, a unified description of chromatin folding comprising various experimental results is still lacking.  After showing that the theory of compact polymers is inconsistent with experimental data, we develop a new model for chromatin based on probabilistic formation of loops. This Random-Loop-Model correctly describes folding into a confined sub-space of the nucleus as well as the observed cell-to-cell variation, suggesting a close relation between expression-dependent compaction and local variations in the looping probabilities. We find that formation of loops is highly beneficial for the nucleus to maintain order and to accomplish entropy-driven segregation of chromosomes. A dynamic model is proposed, showing that the formation of loops can be accomplished solely on the basis of diffusional motion without invoking active mechanisms. Such a dynamic model provides a unified explanatory framework of chromatin folding, yielding testable predictions, which for the first time consistently explain many experimental findings.