Spatial confinement is a major determinant of the folding landscape of human chromosomes.
Bottom Line: Here we describe a model called constrained self-avoiding chromatin (C-SAC) for studying spatial structures of chromosomes, as the available space is a key determinant of chromosome folding.We show that the equilibrium ensemble of randomly folded chromosomes in the confined nuclear volume gives rise to the experimentally observed higher-order architecture of human chromosomes, including average scaling properties of mean-square spatial distance, end-to-end distance, contact probability and their chromosome-to-chromosome variabilities.Our results indicate that the overall structure of a human chromosome is dictated by the spatial confinement of the nuclear space, which may undergo significant tissue- and developmental stage-specific size changes.
Affiliation: Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60607, USA.Show MeSH
Mentions: Our results showed that there is virtually no change in the scaling exponents α and ν in C-SAC chains after introducing binders compared to the original C-SAC chains, where the only constraint is the spatial confinement of the cell nucleus (Figure 4). These results indicate that random self-avoiding chromatin chains folded inside a confined space have an intrinsic propensity to form loops, without the explicit introduction of additional binders. Overall, our results indicate that the confinement at the scale D is the dominant factor in determining the average scaling behavior of chromatin structures.
Affiliation: Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60607, USA.