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bioRxiv · 10.1101/704957

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

Belaghzal, H.·Borrman, T.·Stephens, A. D.·Lafontaine, D. L.·Venev, S. V.·Marko, J. F.·Weng, Z.·Dekker, J.
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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.\n\nHighlightsO_LILiquid chromatin Hi-C detects chromatin interaction dissociation rates genome-wide\nC_LIO_LIChromatin conformations in distinct nuclear compartments differ in stability\nC_LIO_LIStable heterochromatic associations are major drivers of chromatin phase separation\nC_LIO_LICTCF-CTCF loops are stabilized by encirclement of loop bases by cohesin rings\nC_LI

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Belaghzal, H., Borrman, T., Stephens, A. D., Lafontaine, D. L., Venev, S. V., Marko, J. F., Weng, Z., Dekker, J.. 2019-07-16. Compartment-dependent chromatin interaction dynamics revealed by liquid chromatin Hi-C. https://doi.org/10.1101/704957

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