Structure and dynamics of interphase chromosomes.
Structure and dynamics of interphase chromosomes.
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DOI：
10.1371/journal.pcbi.1000153
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发表时间：
2008-08-22
影响因子：
4.3
通讯作者：
Everaers, Ralf
中科院分区：
文献类型：
--
作者：
Rosa, Angelo;Everaers, Ralf
在分裂间期，染色体的密度降低，但荧光原位杂交实验显示，在大多数真核细胞的细胞核内存在着由单个染色体占据的不同区域。我们使用计算机模拟表明，领土的存在和稳定性是一种动力学效应，可以解释，而不调用底层的核支架或DNA序列之间的蛋白质介导的相互作用。特别是，我们表明，实验观察到的领土形状和标记的染色体位点之间的空间距离为人类，果蝇，和芽殖酵母染色体可以复制由一个无参数的最小模型的解压缩染色体。我们的研究结果表明，所观察到的相间结构和动力学是由于一般的聚合物效应：受限布朗运动保存本地的长链分子的拓扑状态和隔离的相互未纠缠的链由于拓扑约束。真核生物的基因组是由染色体组成的。每条染色体由一个连续的DNA双螺旋和相关的蛋白质组成，这些蛋白质以染色质纤维的形式局部组织。在细胞分裂（有丝分裂）期间，染色体采取适合运输的紧凑形式。在正常细胞活动期间（间期），它们在细胞核内解除致密。作为长链分子（在人类染色体的情况下，染色质纤维的轮廓长度约为1 mm），间期染色质纤维的随机热运动受到缠结的阻碍，类似于限制羊毛打结球的操纵。我们使用计算机模拟研究了这种效应的后果。最重要的是，我们发现纠缠效应导致足够长的染色体在间期保持分离并形成“领土”。我们的模型（1）再现了目前可用的实验结果，领土的存在和形状，以及内部的染色体结构和动力学在间期核和（2）解释为什么纠缠效应不干扰染色体凝聚在间期结束时的逆过程。
During interphase chromosomes decondense, but fluorescent in situ hybridization experiments reveal the existence of distinct territories occupied by individual chromosomes inside the nuclei of most eukaryotic cells. We use computer simulations to show that the existence and stability of territories is a kinetic effect that can be explained without invoking an underlying nuclear scaffold or protein-mediated interactions between DNA sequences. In particular, we show that the experimentally observed territory shapes and spatial distances between marked chromosome sites for human, Drosophila, and budding yeast chromosomes can be reproduced by a parameter-free minimal model of decondensing chromosomes. Our results suggest that the observed interphase structure and dynamics are due to generic polymer effects: confined Brownian motion conserving the local topological state of long chain molecules and segregation of mutually unentangled chains due to topological constraints. Eukaryotic genomes are organized in sets of chromosomes. Each chromosome consists of a single continuous DNA double-helix and associated proteins that organize locally in the form of a chromatin fiber. During cell division (mitosis) chromosomes adopt a compact form that is suitable for transport. During periods of normal cell activity (interphase), they decondense inside the cell nucleus. Being long-chain molecules (in the case of human chromosomes the contour length of the chromatin fiber is on the order of 1 mm), the random thermal motion of interphase chromatin fibers is hindered by entanglements, similar to those restricting the manipulation of a knotted ball of wool. We have studied the consequences of this effect using computer simulations. Most importantly, we find that entanglement effects cause sufficiently long chromosomes to remain segregated during interphase and to form “territories.” Our model (1) reproduces currently avaliable experimental results for the existence and shape of territories as well as for the internal chromosome structure and dynamics in interphase nuclei and (2) explains why entanglement effects do not interfere with the reverse process of chromosome condensation at the end of interphase.
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DOI：
10.1083/jcb.141.1.5
发表时间：
1998-04-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fung JC;Marshall WF;Dernburg A;Agard DA;Sedat JW
通讯作者：
Sedat JW
影响因子：
8.6
作者：
DUERING, ER;KREMER, K;GREST, GS
通讯作者：
GREST, GS
影响因子：
56.9
作者：
Everaers, R;Sukumaran, SK;Kremer, K
通讯作者：
Kremer, K
影响因子：
5.5
作者：
FARGE, E;MAGGS, AC
通讯作者：
MAGGS, AC
影响因子：
4.4
作者：
DEGENNES, PG
通讯作者：
DEGENNES, PG