Structural Modeling of Chromatin Integrates Genome Features and Reveals Chromosome Folding Principle

Abstract

How chromosomes fold into 3D structures and how genome functions are affected or even controlled by their spatial organization remain challenging questions. Hi-C experiment has provided important structural insights for chromosome, and Hi-C data are used here to construct the 3D chromatin structure which are characterized by two spatially segregated chromatin compartments A and B. By mapping a plethora of genome features onto the constructed 3D chromatin model, we show vividly the close connection between genome properties and the spatial organization of chromatin. We are able to dissect the whole chromatin into two types of chromatin domains which have clearly different Hi-C contact patterns as well as different sizes of chromatin loops. The two chromatin types can be respectively regarded as the basic units of chromatin compartments A and B, and also spatially segregate from each other as the two chromatin compartments. Therefore, the chromatin loops segregate in the space according to their sizes, suggesting the excluded volume or entropic effect in chromatin compartmentalization as well as chromosome positioning. Taken together, these results provide clues to the folding principles of chromosomes, their spatial organization, and the resulted clustering of many genome features in the 3D space.