近日,
研究人员利用超分辨率活细胞成像技术直接观察了小鼠胚胎干细胞中Fbn2拓扑关联域(TAD)的染色质环,并通过贝叶斯推理对环的动态进行了量化。出乎意料的是,Fbn2环既罕见又动态,成环部分约为3-6.5%,环寿命中值约为10-30分钟。
这些研究结果表明,Fbn2的TAD是高度动态的,其中~92%的时间粘连蛋白挤压的环存在于TAD内,没有桥接两个CTCF的边界。这表明,单一的CTCF边界而不是完全的CTCF-CTCF环状态,可能是功能相互作用的主要调节因素。
Title: Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging
Author: Michele Gabriele, Hugo B. Brando, Simon Grosse-Holz, Asmita Jha, Gina M. Dailey, Claudia Cattoglio, Tsung-Han S. Hsieh, Leonid Mirny, Christoph Zechner, Anders S. Hansen
Issue&Volume: 2022-04-14
Abstract: 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.
DOI: abn6583
Source: https://www.science.org/doi/10.1126/science.abn6583