Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging.

Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging.
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DOI:
10.1126/science.abn6583
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发表时间:
2022-04-29
期刊:
Science (New York, N.Y.)
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其他
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动物基因组通过CTCF和环挤压粘附素折叠成环和拓扑关联结构域(TADs),但环的形成和稳定性的动态机制尚不清楚。在这里,我们使用超分辨率活细胞成像直接可视化小鼠胚胎干细胞中Fbn 2位点的染色质循环,并通过贝叶斯推理量化循环动力学。出乎意料的是,Fbn 2循环是罕见的和动态的,循环分数为~3-6.5%,循环寿命的中位数为~10-30分钟。我们的研究结果表明,Fbn 2肌层是高度动态的,其中~92%的时间内的凝聚素挤出循环存在于肌层内,而不桥接两个CTCF边界。这表明,单一的CTCF边界,而不是完整的CTCF-CTCF循环状态可能是功能相互作用的主要调节器。CTCF/粘附素介导的染色质环的超分辨率活细胞成像揭示这些环是罕见的和动态的。
Animal genomes are folded into loops and topologically associating domains (TADs) by CTCF and loop extruding cohesins, but the live dynamics of loop formation and stability remain unknown. Here, we directly visualize chromatin looping at the Fbn2 TAD in mouse embryonic stem cells using super-resolution live-cell imaging and quantify looping dynamics by Bayesian inference. Unexpectedly, the Fbn2 loop is both rare and dynamic, with a looped fraction of ~3-6.5% and a median loop lifetime of ~10-30 min. Our results establish that the Fbn2 TAD is highly dynamic, where ~92% of the time cohesin-extruded loops exist within the TAD without bridging both CTCF boundaries. This suggests that single CTCF boundaries rather than the fully CTCF-CTCF looped state may be the primary regulators of functional interactions. Super-resolution live-cell imaging of CTCF/cohesin-mediated chromatin loops reveal these loops to be rare and dynamic.
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期刊: Science (New York, N.Y.)
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