Program in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA.
Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA, USA.
Nat Genet. 2021 Mar;53(3):367-378. doi: 10.1038/s41588-021-00784-4. Epub 2021 Feb 11.
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.
活质和失活质的核区隔化被认为是通过相似类型的基因座之间的相互作用介导的微分离发生的。这些相互作用的性质和动态尚不清楚。我们开发了液体染色质 Hi-C 来绘制基因座之间关联稳定性的图谱。在固定和 Hi-C 之前，染色体被碎片化，这消除了强聚合约束，从而能够检测到内在的基因座-基因座相互作用稳定性。当片段大于 10-25kb 时，区隔化是稳定的。将染色质片段化为小于 6kb 的片段会导致基因组组织逐渐丧失。层粘连蛋白相关结构域最稳定，而斑点和多梳相关基因座的相互作用则更具动态性。着丝粒蛋白介导的环在片段化后溶解。液体染色质 Hi-C 提供了染色体相互作用动力学的全基因组视图。
