徐炳祥 (2024-06-30 14:57):
#paper doi:10.1038/s41588-021-00784-4 Nature genetics, 2021, Liquid chromatin Hi-C characterizes compartment-dependent chromatin interaction dynamics。对染色质区室结构(chromatin compartments)的识别是三维基因组学研究的重要课题。本研究中作者基于Flory–Huggins聚合物理论预言了在染色质构象捕获实验中,检测到不同位于不同区室的染色质片段聚合倾向与片段长度和相同/不同区室片段聚合能差异之乘积成正比。在此理论指导下,作者指出实验前预先对基因组施以不同时间的酶解,进而控制片段化后染色质长度,便可在不同水平和维度检查染色质区室结构。作者发现过度预酶解可导致实验无法检测区室和染色质环结构,与核纤层关联的结构域对预酶解是稳定的,而与核斑或多数蛋白有关的结构与对预酶解是敏感的。本研究为染色质构象捕获实验的动力学提供了一个新架构,也为解释一些实验现象提供了新思路。
IF:31.700Q1 Nature genetics, 2021-03. DOI: 10.1038/s41588-021-00784-4 PMID: 33574602
Liquid chromatin Hi-C characterizes compartment-dependent chromatin interaction dynamics
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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.
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