A biophysical model of higher-order chromatin architecture

Energy consuming processes are important in determining the large-scale organization of chromatin. Experiments indicate that chromosomes are organized  in a non-random manner and occupy specific regions of a nucleus, called chromosome territories (CTs), with gene rich regions (euchromatin) more centrally positioned than gene-poor (heterochromatin) regions. Further, chromosomes are largely seen to be positioned radially by gene density, although positioning by chromosomes size is also seen. Our model for large-scale nuclear architecture incorporates the effects of non-equilibrium processes driven by the consumption of ATP, associated to cell-type specific transcriptional processes that are inhomogeneous within and across chromosomes. It yields predictions which compare favorably to experimental data including statistics of positional distributions, shapes and overlaps of each chromosome. Our simulation also reproduce common organizing principles underlying large-scale nuclear architecture across interphase human cell nucleus. These include the differential positioning of two X chromosomes in female cells, the territorial organisation of chromosomes including both gene-density-based and size-based chromosome radial positioning schemes, statistics of the shape of chromosomes, and contact probabilities of individual chromosomes. We proposed that biophysical consequences of the distribution of transcriptional activity across chromosomes should be central to any chromosome positioning code.