Nanoscale mapping of DNA dynamics reveals activity-driven genome organization in living human cells

Nanoscale mapping of DNA dynamics reveals activity-driven genome organization in living human cells
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DNA 动力学的纳米级绘图揭示了人类活细胞中活动驱动的基因组组织

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通讯作者:
Kerstin Bystricky
Kerstin Bystricky
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作者:
H. Shaban;R. Barth;Kerstin Bystricky

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基因组折叠的原理及其与功能的关系取决于对染色质纤维构象变化的理解。目前仍缺乏高分辨率的整体染色质运动分析。我们开发了Hi-D,一种从实时荧光图像同时定量绘制整个细胞核上每个像素的DNA动态的方法。Hi-D结合了利用计算机视觉重建染色质运动和利用贝叶斯推理对局部扩散过程进行分类。我们发现细胞核内部的DNA动力学在空间上被组织成0.3 - 3 μ m的不同类型的扩散域,与染色质压实不耦合。静止细胞和活跃细胞之间动态结构域网络的重组表明微环境在随机染色质运动中起主导作用。Hi-D为理解染色质组织开辟了新的视角,将核分子的整体运动置于核结构的背景下。
Principles of genome folding and their relationship to function depend on understanding conformational changes of the chromatin fiber. Analysis of bulk chromatin motion at high resolution is still lacking. We developed Hi-D, a method to quantitatively map DNA dynamics for every pixel simultaneously over the entire nucleus from real-time fluorescence images. Hi-D combines reconstruction of chromatin motion using computer vision and classification of local diffusion processes by Bayesian inference. We found that DNA dynamics in the nuclear interior are spatially organized into 0.3 – 3 µm domains of distinct types of diffusion was uncoupled from chromatin compaction. Reorganization of the network of dynamic domains between quiescent and active cells suggest that the microenvironment plays a predominant role in stochastic chromatin motion. Hi-D opens new perspectives towards understanding of chromatin organization placing global motion of nuclear molecules in the context of nuclear architecture.
DOI: 10.1529/biophysj.105.066670
发表时间: 2005-12-01
影响因子: 3.4
作者:
Levi, V;Ruan, QQ;Gratton, E
通讯作者: Gratton, E