Compartment-dependent chromatin interaction dynamics revealed by liquid chromatin Hi-C

Houda Belaghzal, Tyler Borrman, Andrew D. Stephens, Denis L. Lafontaine, Sergey V. Venev, Zhiping Weng, John F. Marko, Job Dekker*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Chromosomes are folded so that active and inactive chromatin domains are spatially segregated. Compartmentalization is thought to occur through polymer phase/microphase separation mediated by interactions between loci of similar type. The nature and dynamics of these interactions are not known. We developed liquid chromatin Hi-C to map the stability of associations between loci. Before fixation and Hi-C, chromosomes are fragmented removing the strong polymeric constraint to enable detection of intrinsic locus-locus interaction stabilities. Compartmentalization is stable when fragments are over 10-25 kb. Fragmenting chromatin into pieces smaller than 6 kb leads to gradual loss of genome organization. Dissolution kinetics of chromatin interactions vary for different chromatin domains. Lamin-associated domains are most stable, while interactions among speckle and polycomb-associated loci are more dynamic. Cohesin-mediated loops dissolve after fragmentation, possibly because cohesin rings slide off nearby DNA ends. Liquid chromatin Hi-C provides a genome-wide view of chromosome interaction dynamics.Liquid chromatin Hi-C detects chromatin interaction dissociation rates genome-wideChromatin conformations in distinct nuclear compartments differ in stabilityStable heterochromatic associations are major drivers of chromatin phase separationCTCF-CTCF loops are stabilized by encirclement of loop bases by cohesin rings

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StatePublished - Jul 16 2019

Keywords

  • chromatin dynamics
  • chromatin looping
  • Chromosome compartmentalization
  • copolymer
  • microphase
  • nuclear body
  • nuclear organization
  • phase separation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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