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A DNA Sequence Based Polymer Model for Chromatin Folding

The recent development of sequencing technology and imaging methods has provided an unprecedented understanding of the inter-phase chromatin folding in mammalian nuclei. It was found that chromatin folds into topological-associated domains (TADs) of hundreds of kilo base pairs (kbps), and is further...

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Autores principales: Zhou, Rui, Gao, Yi Qin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865792/
https://www.ncbi.nlm.nih.gov/pubmed/33572740
http://dx.doi.org/10.3390/ijms22031328
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author Zhou, Rui
Gao, Yi Qin
author_facet Zhou, Rui
Gao, Yi Qin
author_sort Zhou, Rui
collection PubMed
description The recent development of sequencing technology and imaging methods has provided an unprecedented understanding of the inter-phase chromatin folding in mammalian nuclei. It was found that chromatin folds into topological-associated domains (TADs) of hundreds of kilo base pairs (kbps), and is further divided into spatially segregated compartments (A and B). The compartment B tends to be located near to the periphery or the nuclear center and interacts with other domains of compartments B, while compartment A tends to be located between compartment B and interacts inside the domains. These spatial domains are found to highly correlate with the mosaic CpG island (CGI) density. High CGI density corresponds to compartments A and small TADs, and vice versa. The variation of contact probability as a function of sequential distance roughly follows a power-law decay. Different chromosomes tend to segregate to occupy different chromosome territories. A model that can integrate these properties at multiple length scales and match many aspects is highly desired. Here, we report a DNA-sequence based coarse-grained block copolymer model that considers different interactions between blocks of different CGI density, interactions of TAD formation, as well as interactions between chromatin and the nuclear envelope. This model captures the various single-chromosome properties and partially reproduces the formation of chromosome territories.
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spelling pubmed-78657922021-02-07 A DNA Sequence Based Polymer Model for Chromatin Folding Zhou, Rui Gao, Yi Qin Int J Mol Sci Article The recent development of sequencing technology and imaging methods has provided an unprecedented understanding of the inter-phase chromatin folding in mammalian nuclei. It was found that chromatin folds into topological-associated domains (TADs) of hundreds of kilo base pairs (kbps), and is further divided into spatially segregated compartments (A and B). The compartment B tends to be located near to the periphery or the nuclear center and interacts with other domains of compartments B, while compartment A tends to be located between compartment B and interacts inside the domains. These spatial domains are found to highly correlate with the mosaic CpG island (CGI) density. High CGI density corresponds to compartments A and small TADs, and vice versa. The variation of contact probability as a function of sequential distance roughly follows a power-law decay. Different chromosomes tend to segregate to occupy different chromosome territories. A model that can integrate these properties at multiple length scales and match many aspects is highly desired. Here, we report a DNA-sequence based coarse-grained block copolymer model that considers different interactions between blocks of different CGI density, interactions of TAD formation, as well as interactions between chromatin and the nuclear envelope. This model captures the various single-chromosome properties and partially reproduces the formation of chromosome territories. MDPI 2021-01-29 /pmc/articles/PMC7865792/ /pubmed/33572740 http://dx.doi.org/10.3390/ijms22031328 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhou, Rui
Gao, Yi Qin
A DNA Sequence Based Polymer Model for Chromatin Folding
title A DNA Sequence Based Polymer Model for Chromatin Folding
title_full A DNA Sequence Based Polymer Model for Chromatin Folding
title_fullStr A DNA Sequence Based Polymer Model for Chromatin Folding
title_full_unstemmed A DNA Sequence Based Polymer Model for Chromatin Folding
title_short A DNA Sequence Based Polymer Model for Chromatin Folding
title_sort dna sequence based polymer model for chromatin folding
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865792/
https://www.ncbi.nlm.nih.gov/pubmed/33572740
http://dx.doi.org/10.3390/ijms22031328
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