Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
University of Basel, Basel, Switzerland.
Nat Genet. 2022 Dec;54(12):1907-1918. doi: 10.1038/s41588-022-01232-7. Epub 2022 Dec 5.
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 10 min. 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.
在哺乳动物中，拓扑关联域内序列的相互作用能够在很大的基因组距离上控制基因表达。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。通过在活细胞中以高时空分辨率成像染色体位置，我们表明拓扑关联域内的相互作用是短暂的，并且在细胞周期的过程中频繁发生。在存在会聚的 CTCF 位点的情况下，相互作用变得更加频繁和持久，从而抑制了染色体折叠随时间的变化。我们的数据支持染色体动力学的物理模型，表明 CTCF 锚定的环持续约 10 分钟。我们的结果表明，长距离转录调控可能依赖于短暂的物理接近，黏连蛋白和 CTCF 稳定高度动态的染色体结构，促进了染色体相互作用的选定子集。
