Differences in the intrinsic spatial dynamics of the chromatin contribute to cell differentiation

Nucleic Acids Res. 2020 Feb 20;48(3):1131-1145. doi: 10.1093/nar/gkz1102.

Abstract

Advances in chromosome conformation capture techniques as well as computational characterization of genomic loci structural dynamics open new opportunities for exploring the mechanistic aspects of genome-scale differences across different cell types. We examined here the dynamic basis of variabilities between different cell types by investigating their chromatin mobility profiles inferred from Hi-C data using an elastic network model representation of the chromatin. Our comparative analysis of sixteen cell lines reveals close similarities between chromosomal dynamics across different cell lines on a global scale, but notable cell-specific variations emerge in the detailed spatial mobilities of genomic loci. Closer examination reveals that the differences in spatial dynamics mainly originate from the difference in the frequencies of their intrinsically accessible modes of motion. Thus, even though the chromosomes of different types of cells have access to similar modes of collective movements, not all modes are deployed by all cells, such that the effective mobilities and cross-correlations of genomic loci are cell-type-specific. Comparison with RNA-seq expression data reveals a strong overlap between highly expressed genes and those distinguished by high mobilities in the present study, in support of the role of the intrinsic spatial dynamics of chromatin as a determinant of cell differentiation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Differentiation / genetics*
  • Cell Line
  • Chromatin / chemistry*
  • Gene Expression
  • Genetic Loci
  • Genome
  • Humans

Substances

  • Chromatin