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从多重荧光原位杂交数据推断间期染色体结构:来自人类和小鼠细胞的统一图景。

Inferring interphase chromosomal structure from multiplexed fluorescence in situ hybridization data: A unified picture from human and mouse cells.

作者信息

Remini Loucif, Segers Midas, Parmeggiani Andrea, Carlon Enrico

机构信息

Laboratoire Charles Coulomb (L2C), Univ Montpellier, CNRS, Montpellier, France.

Soft Matter and Biophysics, KU Leuven, Celestijnenlaan 200D, 3001 Leuven, Belgium.

出版信息

J Chem Phys. 2025 Feb 7;162(5). doi: 10.1063/5.0236067.

Abstract

We analyze multiplexed fluorescence in situ hybridization (m-FISH) data for human and mouse cell lines. The m-FISH technique uses fluorescently-labeled single-stranded probes which hybridize to specific chromosomal regions, thereby allowing the measurement of the spatial positions of up to ∼100 tagged sites for several thousands of interphase chromosomes. Our analysis focuses on a wide range of different cell lines and two distinct organisms and provides a unified picture of chromatin structure for scales ranging from 5 kb (kilobases) up to 2 Mb (megabases), thus covering a genomic region of almost three orders of magnitude. Confirming recent analysis [Remini et al., Phys. Rev. E 109, 024408 (2024)], we show that there are two characteristic arrangements of chromatin referred to as phase α (crumpled globule) and phase β (looped domain) and discuss the physical properties of these phases. We show that a simple heterogeneous random walk model captures the main behavior observed in experiments and brings considerable insights into chromosomal structure.

摘要

我们分析了人类和小鼠细胞系的多重荧光原位杂交(m-FISH)数据。m-FISH技术使用荧光标记的单链探针,这些探针与特定的染色体区域杂交,从而能够测量数千个间期染色体上多达约100个标记位点的空间位置。我们的分析聚焦于广泛的不同细胞系和两种不同的生物体,并提供了一个从5千碱基(kb)到2兆碱基(Mb)范围内染色质结构的统一图景,从而覆盖了近三个数量级的基因组区域。证实了最近的分析[雷米尼等人,《物理评论E》109, 024408 (2024)],我们表明染色质存在两种特征性排列,分别称为α相(皱缩球体)和β相(环状结构域),并讨论了这些相的物理性质。我们表明,一个简单的非均匀随机游走模型捕捉到了实验中观察到的主要行为,并为染色体结构带来了相当多的见解。

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