Chromosome compartmentalization replacement during stem cell differentiation

Abstract

In this paper, changes in a large-scale 3D structure of chromosomes during stem cell differentiation is studied. The polymer coarse-grained model of a human interphase chromosome is introduced which reproduces the experimental Hi-C contact maps in chromosomes 12, 17 for both embryonic stem and differentiated cells with high accuracy.Model based analysis of Hi-C data suggests a mechanism of establishment of preferential longrange chromosomal contacts and compartmentalization replacement during cell stem differentiation. The model provides the conceptual basis for integration of data on the dynamics of chromatin interactions, the 3D structure of chromosomes and gene expression during stem cell differentiation or reprogramming.

Highly heterogeneous long-range interactions explain chromosome compartmentalization

“…The former is the same for all pairs of subunits, while the latter depends on the position of the subunits along the chain. This is similar to the method developed by us in [2,3].…”

“…To test the descriptive capacity of the heterogeneous chromosome model, we used contact maps of chromosome 22 in GM12878 cells at higher resolution than previously used [3]. Fig.1 shows the results of comparison between simulated and experimental [2] contact maps with different resolutions.…”

“…In [3,4] we introduced a completely heteropolymer model of chromosomes, where all potentials between any polymer chain elements are different. The calculations with 100 kilo base pairs (kbp) resolution showed quite good ability of the model to capture the main properties of contact maps, observed in Hi-C experiments.…”

“…The distinct feature of model [3] is that it does not suggest that the genome/chromosome is partitioned into two [1] or six [2] types of compartments or subcompartments equivalent to two or six types of blocks of monomers. In [3,4] and in the present paper we explore the heterogeneous polymer where all subunits are assumed to be different and interaction energies between any pair of elements are different.…”

“…The distinct feature of model [3] is that it does not suggest that the genome/chromosome is partitioned into two [1] or six [2] types of compartments or subcompartments equivalent to two or six types of blocks of monomers. In [3,4] and in the present paper we explore the heterogeneous polymer where all subunits are assumed to be different and interaction energies between any pair of elements are different. To investigate the model’s ability to describe chromosome contact Hi-C data we calculate whole-chromosome contact maps with 50 and 10 kb resolution and compare the quality of description of experimental maps with respect to a polymer model with two to six types of chromatin subunits, or subcompartments, based on the idea of microphase separation.…”