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Physics-based polymer models to probe chromosome structure in single molecules

Item Type:Article
Title:Physics-based polymer models to probe chromosome structure in single molecules
Creators Name:Conte, M. and Chiariello, A.M. and Bianco, S. and Esposito, A. and Abraham, A. and Nicodemi, M.
Abstract:Human chromosomes have a complex 3D spatial organization in the cell nucleus, which comprises a hierarchy of physical interactions across genomic scales. Such an architecture serves important functional roles, as genes and their regulators have to physically interact to control gene regulation. However, the molecular mechanisms underlying the formation of those contacts remain poorly understood. Here, we describe a polymer-physics-based approach to investigate the machinery shaping genome folding and function. In silico model predictions on DNA single-molecule 3D structures are validated against independent super-resolution single-cell microscopy data, supporting a scenario whereby chromosome architecture is controlled by thermodynamics mechanisms of phase separation. Finally, as an application of our methods, the validated single-polymer conformations of the theory are used to benchmark powerful technologies to probe genome structure, such as Hi-C, SPRITE, and GAM.
Keywords:Chromosome Architecture, Gene Regulation, Polymer Physics, Machine Learning, Statistical Mechanics, Phase Separation
Source:Methods in Molecular Biology
Series Name:Methods in Molecular Biology
Title of Book:Polycomb group proteins : methods and protocols
Publisher:Springer / Humana Press
Page Range:57-66
Official Publication:https://doi.org/10.1007/978-1-0716-3143-0_5
PubMed:View item in PubMed

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