Wachsmuth Malte, Knoch Tobias A, Rippe Karsten
Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Biophysical Genomics Group, Department of Cell Biology and Genetics, Erasmus Medical Center, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
Epigenetics Chromatin. 2016 Dec 24;9:57. doi: 10.1186/s13072-016-0093-1. eCollection 2016.
Genome organization into subchromosomal topologically associating domains (TADs) is linked to cell-type-specific gene expression programs. However, dynamic properties of such domains remain elusive, and it is unclear how domain plasticity modulates genomic accessibility for soluble factors.
Here, we combine and compare a high-resolution topology analysis of interacting chromatin loci with fluorescence correlation spectroscopy measurements of domain dynamics in single living cells. We identify topologically and dynamically independent chromatin domains of ~1 Mb in size that are best described by a loop-cluster polymer model. Hydrodynamic relaxation times and gyration radii of domains are larger for open (161 ± 15 ms, 297 ± 9 nm) than for dense chromatin (88 ± 7 ms, 243 ± 6 nm) and increase globally upon chromatin hyperacetylation or ATP depletion.
Based on the domain structure and dynamics measurements, we propose a loop-cluster model for chromatin domains. It suggests that the regulation of chromatin accessibility for soluble factors displays a significantly stronger dependence on factor concentration than search processes within a static network.
基因组组织成亚染色体拓扑相关结构域（TADs）与细胞类型特异性基因表达程序相关。然而，这些结构域的动态特性仍然难以捉摸，并且尚不清楚结构域可塑性如何调节可溶性因子对基因组的可及性。
在这里，我们将相互作用染色质位点的高分辨率拓扑分析与单个活细胞中结构域动态的荧光相关光谱测量相结合并进行比较。我们鉴定出大小约为1 Mb的拓扑和动态独立的染色质结构域，其最佳描述为环簇聚合物模型。开放染色质（161±15毫秒，297±9纳米）的结构域的流体动力学弛豫时间和回转半径大于致密染色质（88±7毫秒，243±6纳米），并且在染色质超乙酰化或ATP耗竭时整体增加。
基于结构域结构和动态测量，我们提出了一种染色质结构域的环簇模型。这表明可溶性因子对染色质可及性的调节对因子浓度的依赖性比对静态网络内搜索过程的依赖性要强得多。
