3D structures of individual mammalian genomes studied by single-cell Hi-C

Nature. 2017 Apr 6;544(7648):59-64. doi: 10.1038/nature21429. Epub 2017 Mar 13.

Abstract

The folding of genomic DNA from the beads-on-a-string-like structure of nucleosomes into higher-order assemblies is crucially linked to nuclear processes. Here we calculate 3D structures of entire mammalian genomes using data from a new chromosome conformation capture procedure that allows us to first image and then process single cells. The technique enables genome folding to be examined at a scale of less than 100 kb, and chromosome structures to be validated. The structures of individual topological-associated domains and loops vary substantially from cell to cell. By contrast, A and B compartments, lamina-associated domains and active enhancers and promoters are organized in a consistent way on a genome-wide basis in every cell, suggesting that they could drive chromosome and genome folding. By studying genes regulated by pluripotency factor and nucleosome remodelling deacetylase (NuRD), we illustrate how the determination of single-cell genome structure provides a new approach for investigating biological processes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Animals
  • CCCTC-Binding Factor
  • Cell Cycle Proteins / metabolism
  • Chromatin Assembly and Disassembly* / genetics
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosomes, Mammalian / chemistry
  • Chromosomes, Mammalian / genetics
  • Chromosomes, Mammalian / metabolism
  • Cohesins
  • DNA / chemistry
  • DNA / genetics
  • DNA / metabolism
  • Enhancer Elements, Genetic
  • G1 Phase
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Genome* / genetics
  • Haploidy
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex / metabolism
  • Mice
  • Models, Molecular
  • Molecular Conformation
  • Molecular Imaging / methods*
  • Molecular Imaging / standards
  • Mouse Embryonic Stem Cells / cytology
  • Mouse Embryonic Stem Cells / metabolism
  • Nucleosomes / chemistry*
  • Nucleosomes / genetics
  • Nucleosomes / metabolism
  • Promoter Regions, Genetic
  • Repressor Proteins / metabolism
  • Reproducibility of Results
  • Single-Cell Analysis / methods*
  • Single-Cell Analysis / standards

Substances

  • CCCTC-Binding Factor
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Ctcf protein, mouse
  • Nucleosomes
  • Repressor Proteins
  • DNA
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex