PHi-C: deciphering Hi-C data into polymer dynamics

Abstract Genomes are spatiotemporally organized within the cell nucleus. Genome-wide chromosome conformation capture (Hi-C) technologies have uncovered the 3D genome organization. Furthermore, live-cell imaging experiments have revealed that genomes are functional in 4D. Although computational modeling methods can convert 2D Hi-C data into population-averaged static 3D genome models, exploring 4D genome nature based on 2D Hi-C data remains lacking. Here, we describe a 4D simulation method, PHi-C (polymer dynamics deciphered from Hi-C data), that depicts 4D genome features from 2D Hi-C data by polymer modeling. PHi-C allows users to interpret 2D Hi-C data as physical interaction parameters within single chromosomes. The physical interaction parameters can then be used in the simulations and analyses to demonstrate dynamic characteristics of genomic loci and chromosomes as observed in live-cell imaging experiments. PHi-C is available at https://github.com/soyashinkai/PHi-C.

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PHi-C: deciphering Hi-C data into polymer dynamics

10.1101/574962 ◽

2019 ◽

Cited By ~ 3

Author(s):

Soya Shinkai ◽

Masaki Nakagawa ◽

Takeshi Sugawara ◽

Yuichi Togashi ◽

Hiroshi Ochiai ◽

...

Keyword(s):

Dynamic Characteristics ◽

Live Cell Imaging ◽

Cell Imaging ◽

Computational Modelling ◽

Simulation Method ◽

Polymer Dynamics ◽

Cell Nuclei ◽

3D Genome ◽

Genome Features ◽

Modelling Methods

Computational modelling methods for Hi-C data have revealed averaged and static features of the 3D genome in cell nuclei. Here, we describe a 4D simulation method, PHi-C (Polymer dynamics deciphered from Hi-C data), that depicts dynamic 3D genome features through polymer modelling. This method allows for demonstrations of dynamic characteristics of genomic loci and chromosomes, as observed in live-cell imaging experiments, and provides physical insights into Hi-C data.

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The repressive genome compartment is established early in the cell cycle before forming the lamina associated domains

10.1101/481598 ◽

2018 ◽

Cited By ~ 8

Author(s):

TR Luperchio ◽

MEG Sauria ◽

VE Hoskins ◽

X Wong ◽

E DeBoy ◽

...

Keyword(s):

Live Cell Imaging ◽

Cell Imaging ◽

Regulation Of Gene Expression ◽

Three Dimensional ◽

Nuclear Lamina ◽

Early Event ◽

Chromosome Conformation ◽

3D Genome ◽

Dynamic Relationship ◽

Organizational Principles

AbstractThree-dimensional (3D) genome organization is thought to be important for regulation of gene expression. Chromosome conformation capture-based studies have uncovered ensemble organizational principles such as active (A) and inactive (B) compartmentalization. In addition, large inactive regions of the genome associate with the nuclear lamina, the Lamina Associated Domains (LADs). Here we investigate the dynamic relationship between A/B-compartment organization and the 3D organization of LADs. Using refined algorithms to identify active (A) and inactive (B) compartments from Hi-C data and to define LADs from DamID, we confirm that the LADs correspond to the B-compartment. Using specialized chromosome conformation paints, we show that LAD and A/B-compartment organization are dependent upon chromatin state and A-type lamins. By integrating single-cell Hi-C data with live cell imaging and chromosome conformation paints, we demonstrate that self-organization of the B-compartment within a chromosome is an early event post-mitosis and occurs prior to organization of these domains to the nuclear lamina.

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