Genome-wide chromosome architecture prediction reveals biophysical principles underlying gene structure.

IF 11.1 Q1 CELL BIOLOGY
Cell genomics Pub Date : 2024-12-11 Epub Date: 2024-11-25 DOI:10.1016/j.xgen.2024.100698
Michael Chiang, Chris A Brackley, Catherine Naughton, Ryu-Suke Nozawa, Cleis Battaglia, Davide Marenduzzo, Nick Gilbert
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引用次数: 0

Abstract

Classical observations suggest a connection between 3D gene structure and function, but testing this hypothesis has been challenging due to technical limitations. To explore this, we developed epigenetic highly predictive heteromorphic polymer (e-HiP-HoP), a model based on genome organization principles to predict the 3D structure of human chromatin. We defined a new 3D structural unit, a "topos," which represents the regulatory landscape around gene promoters. Using GM12878 cells, we predicted the 3D structure of over 10,000 active gene topoi and stored them in the 3DGene database. Data mining revealed folding motifs and their link to Gene Ontology features. We computed a structural diversity score and identified influential nodes-chromatin sites that frequently interact with gene promoters, acting as key regulators. These nodes drive structural diversity and are tied to gene function. e-HiP-HoP provides a framework for modeling high-resolution chromatin structure and a mechanistic basis for chromatin contact networks that link 3D gene structure with function.

全基因组染色体结构预测揭示了基因结构的生物物理原理。
经典的观察结果表明,三维基因结构与功能之间存在联系,但由于技术限制,对这一假设的检验一直具有挑战性。为了探索这个问题,我们开发了表观遗传高度预测异形聚合物(e-HiP-HoP),这是一个基于基因组组织原理的模型,用于预测人类染色质的三维结构。我们定义了一种新的三维结构单元--"topos",它代表了基因启动子周围的调控景观。利用 GM12878 细胞,我们预测了 10,000 多个活跃基因拓扑的三维结构,并将其存储在 3DGene 数据库中。数据挖掘揭示了折叠图案及其与基因本体特征的联系。我们计算了结构多样性得分,并确定了有影响力的节点--经常与基因启动子相互作用的染色质位点,它们是关键的调节因子。e-HiP-HoP为高分辨率染色质结构建模提供了一个框架,也为染色质接触网络提供了一个机制基础,从而将三维基因结构与功能联系起来。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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CiteScore
7.10
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