Interphase human chromosome exhibits out of equilibrium glassy dynamics
Interphase human chromosome exhibits out of equilibrium glassy dynamics
复制标题
人类染色体间期表现出不平衡的玻璃态动力学
DOI：
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发表时间：
2017
影响因子：
16.6
通讯作者：
D. Thirumalai
中科院分区：
文献类型：
--
作者：
Guang Shi;Lei Liu;Changbong Hyeon;D. Thirumalai
利用 Hi-C 和成像技术的进步，基因组三维组织的指纹已经出现。然而，人们对基因组动力学知之甚少。在这里，我们通过将染色体表示为具有对应于常染色质和异染色质的两个表观遗传位点类型的共聚物来创建染色体共聚物模型（CCM）。使用新颖的聚类技术，我们定量地确定了 5 号和 10 号染色体的模拟接触图和拓扑关联域 (TAD) 与从 Hi-C 实验推断的结果非常一致。染色质表现出玻璃态动力学，具有微米级的相干运动。各个基因座的扩散指数的广泛分布在数量上与实验一致，表明存在高度异质的动力学。这反映在接触图的单元与单元之间的变化中。染色体组织是分层的，涉及在基因组规模上形成染色体液滴 (CD)，与 TAD 大小一致，然后 CD 合并，让人想起奥斯特瓦尔德成熟。核空间内染色体的 3D 组织对于生物功能非常重要。在这里，作者将染色体建模为具有不同表观遗传状态的自回避共聚物，并表明可以重现实验生成的接触图的特征并预测其动态。
Fingerprints of the three-dimensional organization of genomes have emerged using advances in Hi-C and imaging techniques. However, genome dynamics is poorly understood. Here, we create the chromosome copolymer model (CCM) by representing chromosomes as a copolymer with two epigenetic loci types corresponding to euchromatin and heterochromatin. Using novel clustering techniques, we establish quantitatively that the simulated contact maps and topologically associating domains (TADs) for chromosomes 5 and 10 and those inferred from Hi-C experiments are in good agreement. Chromatin exhibits glassy dynamics with coherent motion on micron scale. The broad distribution of the diffusion exponents of the individual loci, which quantitatively agrees with experiments, is suggestive of highly heterogeneous dynamics. This is reflected in the cell-to-cell variations in the contact maps. Chromosome organization is hierarchical, involving the formation of chromosome droplets (CDs) on genomic scale, coinciding with the TAD size, followed by coalescence of the CDs, reminiscent of Ostwald ripening. The 3D organization of chromosomes within the nuclear space is important for biological functions. Here the authors model chromosomes as self-avoiding copolymers with distinct epigenetic states, and show that the features of experimentally generated contact maps can be reproduced and their dynamics predicted.
影响因子：
3.4
作者：
Levi, V;Ruan, QQ;Gratton, E
通讯作者：
Gratton, E
DOI：
10.1073/pnas.92.7.2710
发表时间：
1995-03-28
影响因子：
11.1
作者：
SACHS, RK;VANDENENGH, G;HEARST, JE
通讯作者：
HEARST, JE