MiOS, an integrated imaging and computational strategy to model gene folding with nucleosome resolution.
MiOS, an integrated imaging and computational strategy to model gene folding with nucleosome resolution.
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DOI：
10.1038/s41594-022-00839-y
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发表时间：
2022-10
影响因子：
16.8
通讯作者：
Cosma, Maria Pia
中科院分区：
文献类型：
--
作者：
Victoria Neguembor, Maria;Pablo Arcon, Juan;Buitrago, Diana;Lema, Rafael;Walther, Jurgen;Garate, Ximena;Martin, Laura;Romero, Pablo;Abed, Jumana AlHaj;Gut, Marta;Blanc, Julie;Lakadamyali, Melike;Wu, Chao-ting;Brun Heath, Isabelle;Orozco, Modesto;Dans, Pablo D.;Cosma, Maria Pia
DNA的线性序列提供了关于基因及其沿染色体调控元件的宝贵信息。然而，为了充分了解基因的功能和调控，我们需要解剖基因在三维核空间中的物理折叠方式。在这里，我们描述了免疫oligostorm (iOS)，这是一种成像策略，通过DNA和组蛋白的同时可视化，以超分辨率显示特定基因内核小体的分布。我们将iOS与基于约束和粗粒度的建模方法相结合，将超分辨率成像数据与Hi-C接触频率和反卷积mnase测序信息相结合。由此产生的方法称为建模免疫寡聚风暴（MiOS），允许对核小体分辨率的基因进行定量建模，并提供有关调控因子（如RNA聚合酶II）的染色质可及性的信息。利用MiOS，我们探索了人类多能和分化细胞中内务管理和多能相关基因的细胞间变异性、转录依赖的基因构象和折叠，从而获得了迄今为止实现的最高程度的数据整合。作者介绍了Modeling immune - oligostorm (MiOS)，这是一种超分辨率成像和计算策略，可以在多个基因组尺度上模拟3D基因折叠，达到单基因水平的核小体分辨率。
The linear sequence of DNA provides invaluable information about genes and their regulatory elements along chromosomes. However, to fully understand gene function and regulation, we need to dissect how genes physically fold in the three-dimensional (3D) nuclear space. Here we describe immuno-OligoSTORM (iOS), an imaging strategy that reveals the distribution of nucleosomes within specific genes in super-resolution, through the simultaneous visualization of DNA and histones. We combine iOS with restraint-based and coarse-grained modeling approaches to integrate super-resolution imaging data with Hi-C contact frequencies and deconvoluted MNase-sequencing information. The resulting method, called Modeling immuno-OligoSTORM (MiOS), allows quantitative modeling of genes with nucleosome resolution and provides information about chromatin accessibility for regulatory factors, such as RNA polymerase II. With MiOS, we explore intercellular variability, transcriptional-dependent gene conformation and folding of housekeeping and pluripotency-related genes in human pluripotent and differentiated cells, thereby obtaining the highest degree of data integration achieved so far. The authors present Modeling immuno-OligoSTORM (MiOS), a super-resolution imaging and computational strategy to model 3D gene folding at multiple genomic scales, reaching nucleosome resolution at the single-gene level.
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影响因子：
48
作者：
Fiorillo L;Musella F;Conte M;Kempfer R;Chiariello AM;Bianco S;Kukalev A;Irastorza-Azcarate I;Esposito A;Abraham A;Prisco A;Pombo A;Nicodemi M
通讯作者：
Nicodemi M
影响因子：
56.9
作者：
Bates, Mark;Huang, Bo;Zhuang, Xiaowei
通讯作者：
Zhuang, Xiaowei
影响因子：
16.6
作者：
Conte, Mattia;Fiorillo, Luca;Nicodemi, Mario
通讯作者：
Nicodemi, Mario
影响因子：
8.8
作者：
Blinka S;Reimer MH Jr;Pulakanti K;Rao S
通讯作者：
Rao S
影响因子：
4
作者：
Di Stefano M;Paulsen J;Jost D;Marti-Renom MA
通讯作者：
Marti-Renom MA