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在压缩的染色体上,一对远端 DNA 位点的随机运动和转录动力学。

Stochastic motion and transcriptional dynamics of pairs of distal DNA loci on a compacted chromosome.

机构信息

Institute of Science and Technology, Am Campus 1, Klosterneuburg, Austria.

School of Life Science and Technology, ShanghaiTech University, Shanghai, China.

出版信息

Science. 2023 Jun 30;380(6652):1357-1362. doi: 10.1126/science.adf5568. Epub 2023 Jun 29.

Abstract

Chromosomes in the eukaryotic nucleus are highly compacted. However, for many functional processes, including transcription initiation, the pairwise motion of distal chromosomal elements such as enhancers and promoters is essential and necessitates dynamic fluidity. Here, we used a live-imaging assay to simultaneously measure the positions of pairs of enhancers and promoters and their transcriptional output while systematically varying the genomic separation between these two DNA loci. Our analysis reveals the coexistence of a compact globular organization and fast subdiffusive dynamics. These combined features cause an anomalous scaling of polymer relaxation times with genomic separation leading to long-ranged correlations. Thus, encounter times of DNA loci are much less dependent on genomic distance than predicted by existing polymer models, with potential consequences for eukaryotic gene expression.

摘要

真核细胞核内的染色体高度压缩。然而,对于许多功能过程,包括转录起始,远端染色体元件如增强子和启动子的成对运动是必不可少的,需要动态流动性。在这里,我们使用活细胞成像测定法同时测量了两对增强子和启动子的位置及其转录产物,同时系统地改变了这两个 DNA 位点之间的基因组分离。我们的分析揭示了紧凑的球形组织和快速亚扩散动力学的共存。这些综合特征导致聚合物弛豫时间与基因组分离的异常标度,导致长程相关性。因此,DNA 位点的相遇时间比现有聚合物模型预测的对基因组距离的依赖性小得多,这对真核基因表达可能有潜在的影响。

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