Defining and detecting links in chromosomes

Sci Rep. 2019 Aug 13;9(1):11753. doi: 10.1038/s41598-019-47999-4.

Abstract

Sophisticated methods for mapping chromatin contacts enable to generate data of the genome structure that provide deep insights into the formation of chromatin interactions within cell nuclei. Due to the recent progress in this field, three-dimensional genomic structures of individual haploid mouse embryonic stem cells have been determined. Here, we analyze these data (8 cells) and determine comprehensive landscape of entanglements between interphase chromosomes. We find a significant number of stable links formed by chromosome pairs. Some links are even conserved between cells. Moreover, examples of stable multiple links, with at least three chromosomes engaged, are also identified. Types of links and their location along chromosomes are determined based on computations of HOMFLY-PT polynomials and Gauss Linking Numbers. Furthermore, stability of links is studied between different models, cells, and based on relaxation simulations of the genomic structure in a simplified structure-based representation. Identified links suggest that small fraction of chromosomes are entangled not only locally. How topoisomerases engineer such configurations remains an open question. Furthermore, presented methods can be used as a quantitative assessment - descriptor - to distinguish the quality of modeled data.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Chromosome Mapping*
  • Genome
  • Humans
  • Interphase
  • Mice