Micron-scale coherence in interphase chromatin dynamics
Micron-scale coherence in interphase chromatin dynamics
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DOI：
10.1073/pnas.1220313110
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发表时间：
2013-09-24
影响因子：
11.1
通讯作者：
Mitchison, Timothy J.
中科院分区：
文献类型：
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作者：
Zidovska, Alexandra;Weitz, David A.;Mitchison, Timothy J.
染色质结构和动力学控制着DNA生物学的各个方面，但人们对其了解甚少，特别是在大长度尺度上。我们开发了一种方法，基于时间分辨图像相关分析的位移相关光谱，在培养的人类细胞中同时绘制整个细胞核的染色质动力学。该方法揭示了染色质在大区域（4-5 μ m）内连续运动数秒。相干运动区域延伸到单染色体区域的边界之外，表明运动在长度尺度上的弹性耦合比基因的大得多。这些大规模的耦合运动是ATP依赖的，并且在几秒钟内是单向的，这可能解释了单个基因依赖ATP的定向运动。主要的核atp酶如DNA聚合酶、RNA聚合酶II和拓扑异构酶II的扰动消除了微米级的一致性，同时引起快速的局部运动增加；也就是说，局部运动加速，但与邻近的运动不耦合。我们在诱导直接DNA损伤时观察到染色质动力学的类似趋势；因此，我们假设这可能是由于DNA损伤反应，物理上放松染色质和阻止远距离通信的力量。
Chromatin structure and dynamics control all aspects of DNA biology yet are poorly understood, especially at large length scales. We developed an approach, displacement correlation spectroscopy based on time-resolved image correlation analysis, to map chromatin dynamics simultaneously across the whole nucleus in cultured human cells. This method revealed that chromatin movement was coherent across large regions (4-5 mu m) for several seconds. Regions of coherent motion extended beyond the boundaries of single-chromosome territories, suggesting elastic coupling of motion over length scales much larger than those of genes. These large-scale, coupled motions were ATP dependent and unidirectional for several seconds, perhaps accounting for ATP-dependent directed movement of single genes. Perturbation of major nuclear ATPases such as DNA polymerase, RNA polymerase II, and topoisomerase II eliminated micron-scale coherence, while causing rapid, local movement to increase; i.e., local motions accelerated but became uncoupled from their neighbors. We observe similar trends in chromatin dynamics upon inducing a direct DNA damage; thus we hypothesize that this may be due to DNA damage responses that physically relax chromatin and block long-distance communication of forces.