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A polymer model explains the complexity of large-scale chromatin folding

机译:聚合物模型解释了大规模染色质折叠的复杂性

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The underlying global organization of chromatin within the cell nucleus has been the focus of intense recent research. Hi-C methods have allowed for the detection of genome-wide chromatin interactions, revealing a complex large-scale organization where chromosomes tend to partition into megabase-sized “topological domains” of local chromatin interactions and intra-chromosomal contacts extends over much longer scales, in a cell-type and chromosome specific manner. Until recently, the distinct chromatin folding properties observed experimentally have been difficult to explain in a single conceptual framework. We reported that a simple polymer-physics model of chromatin, the strings and binders switch (SBS) model, succeeds in describing the full range of chromatin configurations observed in vivo. The SBS model simulates the interactions between randomly diffusing binding molecules and binding sites on a polymer chain. It explains how polymer architectural patterns can be established, how different stable conformations can be produced and how conformational changes can be reliably regulated by simple strategies, such as protein upregulation or epigenetic modifications, via fundamental thermodynamics mechanisms.
机译:细胞核内染色质的潜在全球组织一直是近期研究的重点。 Hi-C方法允许检测全基因组的染色质相互作用,揭示了一个复杂的大规模组织,其中染色体倾向于分配到局部染色质相互作用的兆碱基大小的“拓扑结构域”,并且染色体内接触范围更长。 ,以细胞类型和染色体特定的方式显示。直到最近,通过实验观察到的独特的染色质折叠特性一直难以在单个概念框架中进行解释。我们报道了一个简单的染色质聚合物物理模型,即字符串和粘合剂转换(SBS)模型,成功地描述了体内观察到的染色质构型的全部范围。 SBS模型模拟了随机扩散的结合分子与聚合物链上结合位点之间的相互作用。它解释了如何通过基本的热力学机制,通过简单的策略,例如蛋白质上调或表观遗传修饰,可以建立聚合物的结构模式,如何产生不同的稳定构象,以及如何可靠地调节构象变化。

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