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Higher-order Chromosome Structures Investigated by Polymer Physics in Cellular Morphogenesis and Differentiation

机译:通过聚合物物理学在细胞形态发生和分化中研究的高阶染色体结构

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Experimental advances in Molecular Biology demonstrated that chromatin architecture and gene regulation are deeply related. Hi-C data, for instance, returned a scenario where chromosomes form a complex pattern of interactions, including TADs, metaTADs, and compartments, correlated with genomic and epigenomic features. Here, we discuss the emerging hierarchical organization of chromatin and show how it remains partially conserved during mouse neuronal differentiation with changes highly related to modifications in gene expression. In this scenario, models of polymer physics, such as the Strings & Binders (SBS) model, can be a crucial instrument to understand the molecular mechanisms underlying the formation of such a higher order 3D structure. In particular, we focus on the case study of the murine Pitx1 genomic region. At this locus, two alternative spatial conformations take place in the hindlimb and forelimb tissues, corresponding to two different transcriptional states of Pitxl. We finally show how the structural variants can affect the locus 3D organization leading to ectopic gene expression and limb malformations. (C) 2019 Elsevier Ltd. All rights reserved.
机译:分子生物学的实验进展证明了染色质架构和基因调控深受相关。例如,Hi-C数据返回了染色体形成复杂的相互作用模式的场景,包括TAD,Metatad和隔室,与基因组和表观胶质特征相关。在这里,我们讨论了染色质的新出现的分层组织,并展示了在小鼠神经元分化期间将其在与基因表达中的修饰高度相关的变化期间保持部分保守。在这种情况下,高分子物理学的模型,例如弦和粘合剂(SBS)模型,可以是理解这种更高阶3D结构的形成的分子机制的重要仪器。特别是,我们专注于鼠PITX1基因组区域的案例研究。在该基因座,在后肢和前肢组织中发生两种替代的空间构象,对应于PitX1的两种不同转录状态。我们终于展示了结构变体如何影响轨迹3D组织,导致异位基因表达和肢体畸形。 (c)2019 Elsevier Ltd.保留所有权利。

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