Liquid chromatin Hi-C characterizes compartment-dependent chromatin interaction dynamics

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

doi:10.1038/s41588-021-00784-4

Liquid chromatin Hi-C characterizes compartment-dependent chromatin interaction dynamics

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

Molecular Biosciences

Research output: Contribution to journal › Article › peer-review

49 Scopus citations

Abstract

Nuclear compartmentalization of active and inactive chromatin is thought to occur through 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, which removes strong polymeric constraint, enabling detection of intrinsic locus–locus interaction stabilities. Compartmentalization is stable when fragments are larger than 10–25 kb. Fragmentation of chromatin into pieces smaller than 6 kb leads to gradual loss of genome organization. Lamin-associated domains are most stable, whereas interactions for speckle- and polycomb-associated loci are more dynamic. Cohesin-mediated loops dissolve after fragmentation. Liquid chromatin Hi-C provides a genome-wide view of chromosome interaction dynamics.

Original language	English (US)
Pages (from-to)	367-378
Number of pages	12
Journal	Nature Genetics
Volume	53
Issue number	3
DOIs	https://doi.org/10.1038/s41588-021-00784-4
State	Published - Mar 2021

ASJC Scopus subject areas

Genetics

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title = "Liquid chromatin Hi-C characterizes compartment-dependent chromatin interaction dynamics",

abstract = "Nuclear compartmentalization of active and inactive chromatin is thought to occur through 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, which removes strong polymeric constraint, enabling detection of intrinsic locus–locus interaction stabilities. Compartmentalization is stable when fragments are larger than 10–25 kb. Fragmentation of chromatin into pieces smaller than 6 kb leads to gradual loss of genome organization. Lamin-associated domains are most stable, whereas interactions for speckle- and polycomb-associated loci are more dynamic. Cohesin-mediated loops dissolve after fragmentation. Liquid chromatin Hi-C provides a genome-wide view of chromosome interaction dynamics.",

author = "Houda Belaghzal and Tyler Borrman and Stephens, {Andrew D.} and Lafontaine, {Denis L.} and Venev, {Sergey V.} and Zhiping Weng and Marko, {John F.} and Job Dekker",

note = "Funding Information: J.D. and J.F.M. acknowledge support from the National Institutes of Health Common Fund 4D Nucleome Program (U54-DK107980). This work was also supported by a grant from the National Human Genome Research Institute (NHGRI) to J.D. (HG003143) and to Z.W. (HG009446), and by grants from the National Cancer Institute (U54-CA193419) and from the National Institutes of Health (R01-GM105847 to J.F.M. and K99-GM123195 to A.D.S.). J.D. is an investigator of the Howard Hughes Medical Institute. We thank L. A. Mirny and E. J. Banigan for discussions, and J. Ma for sharing K562 sub-compartment assignments. Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.",

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AU - Weng, Zhiping

AU - Marko, John F.

AU - Dekker, Job

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Liquid chromatin Hi-C characterizes compartment-dependent chromatin interaction dynamics

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