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 language | English (US) |
|---|---|
| Journal | Unknown Journal |
| DOIs | |
| State | Published - 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)