RT Journal Article
SR Electronic
T1 Compartment-dependent chromatin interaction dynamics revealed by liquid chromatin Hi-C
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 704957
DO 10.1101/704957
A1 Houda Belaghzal
A1 Tyler Borrman
A1 Andrew D. Stephens
A1 Denis L. Lafontaine
A1 Sergey V. Venev
A1 Zhiping Weng
A1 John F. Marko
A1 Job Dekker
YR 2019
UL http://biorxiv.org/content/early/2019/07/16/704957.abstract
AB 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.HighlightsLiquid 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