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首页> 外文期刊>Nucleic Acids Research >Modeling epigenome folding: formation and dynamics of topologically associated chromatin domains
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Modeling epigenome folding: formation and dynamics of topologically associated chromatin domains

机译：模拟外形折叠：拓扑相关染色质域的形成和动力学

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摘要

Genomes of eukaryotes are partitioned into domains of functionally distinct chromatin states. These domains are stably inherited across many cell generations and can be remodeled in response to developmental and external cues, hence contributing to the robustness and plasticity of expression patterns and cell phenotypes. Remarkably, recent studies indicate that these 1D epigenomic domains tend to fold into 3D topologically associated domains forming specialized nuclear chromatin compartments. However, the general mechanisms behind such compartmentalization including the contribution of epigenetic regulation remain unclear. Here, we address the question of the coupling between chromatin folding and epigenome. Using polymer physics, we analyze the properties of a block copolymer model that accounts for local epigenomic information. Considering copolymers build from the epigenomic landscape of Drosophila, we observe a very good agreement with the folding patterns observed in chromosome conformation capture experiments. Moreover, this model provides a physical basis for the existence of multistability in epigenome folding at sub-chromosomal scale. We show how experiments are fully consistent with multistable conformations where topologically associated domains of the same epigenomic state interact dynamically with each other. Our approach provides a general framework to improve our understanding of chromatin folding during cell cycle and differentiation and its relation to epigenetics.
机译：真核生物的基因组分配到功能上不同的染色质态的结构域。这些域稳定地围绕许多细胞代群继承，并且可以响应于发育和外部提示来改造，因此有助于表达模式和细胞表型的鲁棒性和可塑性。值得注意的是，最近的研究表明，这些1D表观锥趋于倾向于形成形成专用核染色质室的3D拓扑相关结构域。然而，包括表观遗传监管的贡献的这种分区化背后的一般机制仍不清楚。在这里，我们解决了染色质折叠和外延蛋白组之间的偶联的问题。使用聚合物物理学，我们分析了局部表观群信息的嵌段共聚物模型的性质。考虑从果蝇的表观形式景观中构建的共聚物，我们观察到染色体构象捕获实验中观察到的折叠模式非常好。此外，该模型为亚染色体尺度的外观蛋白折叠折叠中的多用产物提供了物理基础。我们展示了实验如何完全一致地与多个构象完全一致，其中相同表观态的拓扑相关结构域彼此动态地相互作用。我们的方法提供了一般框架，以改善细胞周期和分化期间对染色质折叠的理解及其与表观遗传学的关系。

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