Topological Constraints with Optimal Length Promote the Formation of Chromosomal Territories at Weakened Degree of Phase Separation

JC Wei and H Tian and R Zhou and YF Shao and F Song and YQ Gao, JOURNAL OF PHYSICAL CHEMISTRY B, 125, 9092-9101 (2021).

DOI: 10.1021/acs.jpcb.1c03523

It is generally agreed that the nuclei of eukaryotic cells at interphase are partitioned into disjointed territories, with distinct regions occupied by certain chromosomes. However, the underlying mechanism for such territorialization is still under debate. Here we model chromosomes as coarse-grained block copolymers and to investigate the effect of loop domains (LDs) on the formation of compartments and territories based on dissipative particle dynamics. A critical length of LDs, which depends sensitively on the length of polymeric blocks, is obtained to minimize the degree of phase separation. This also applies to the two-polymer system: The critical length not only maximizes the degree of territorialization but also minimizes the degree of phase separation. Interestingly, by comparing with experimental data, we find the critical length for LDs and the corresponding length of blocks to be respectively very close to the mean length of topologically associating domains (TADs) and chromosomal segments with different densities of CpG islands for human chromosomes. The results indicate that topological constraints with optimal length can contribute to the formation of territories by weakening the degree of phase separation, which likely promotes the chromosomal flexibility in response to genetic regulations.

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