小柯机器人

瑞士弗里德里希·米舍尔生物医学研究所Luca Giorgetti团队近期取得重要工作进展，他们研究发现黏连蛋白和CTCF可以控制染色体折叠的动态变化。该项研究成果2022年12月5日在线发表于《自然—遗传学》杂志上。

据介绍，在哺乳动物拓扑关联域内，序列之间的相互作用能够使远距离的基因表达调控成为可能。然而，目前尚不清楚这种接触发生的频率、持续时间以及它们如何依赖于染色体折叠的动力学和黏连蛋白的环挤出活性。

通过对活细胞中染色体位置进行高空间和时间分辨率成像，研究人员发现，拓扑关联域内的相互作用是短暂的，并且在细胞周期过程中频繁发生。在聚合CTCF位点的存在下，相互作用变得更加频繁和漫长，从而抑制了染色体折叠在不同时期的可变性。在染色体动力学物理模型的支持下，研究数据表明，CTCF锚定的环持续时间约10分钟。

结果表明，长距离的转录调节可能依赖于瞬时的物理接近，并且粘连蛋白和CTCF稳定高度动态的染色体结构，促进选定的染色体互动区域。

附：英文原文

Title: Cohesin and CTCF control the dynamics of chromosome folding

Author: Mach, Pia, Kos, Pavel I., Zhan, Yinxiu, Cramard, Julie, Gaudin, Simon, Tnnermann, Jana, Marchi, Edoardo, Eglinger, Jan, Zuin, Jessica, Kryzhanovska, Mariya, Smallwood, Sebastien, Gelman, Laurent, Roth, Gregory, Nora, Elphge P., Tiana, Guido, Giorgetti, Luca

Issue&Volume: 2022-12-05

Abstract: In mammals, interactions between sequences within topologically associating domains enable control of gene expression across large genomic distances. Yet it is unknown how frequently such contacts occur, how long they last and how they depend on the dynamics of chromosome folding and loop extrusion activity of cohesin. By imaging chromosomal locations at high spatial and temporal resolution in living cells, we show that interactions within topologically associating domains are transient and occur frequently during the course of a cell cycle. Interactions become more frequent and longer in the presence of convergent CTCF sites, resulting in suppression of variability in chromosome folding across time. Supported by physical models of chromosome dynamics, our data suggest that CTCF-anchored loops last around 10min. Our results show that long-range transcriptional regulation might rely on transient physical proximity, and that cohesin and CTCF stabilize highly dynamic chromosome structures, facilitating selected subsets of chromosomal interactions.

DOI: 10.1038/s41588-022-01232-7

Source: https://www.nature.com/articles/s41588-022-01232-7

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex