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Shaping the genome via lengthwise compaction, phase separation, and lamina adhesion
The link between genomic structure and biological function is yet to be consolidated, it is, however, clear that physical manipulation of the genome, driven by the activity of a variety of proteins, is a crucial step. To understand the consequences of the physical forces underlying genome organizati...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9071446/ https://www.ncbi.nlm.nih.gov/pubmed/35420130 http://dx.doi.org/10.1093/nar/gkac231 |
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author | Brahmachari, Sumitabha Contessoto, Vinícius G Di Pierro, Michele Onuchic, José N |
author_facet | Brahmachari, Sumitabha Contessoto, Vinícius G Di Pierro, Michele Onuchic, José N |
author_sort | Brahmachari, Sumitabha |
collection | PubMed |
description | The link between genomic structure and biological function is yet to be consolidated, it is, however, clear that physical manipulation of the genome, driven by the activity of a variety of proteins, is a crucial step. To understand the consequences of the physical forces underlying genome organization, we build a coarse-grained polymer model of the genome, featuring three fundamentally distinct classes of interactions: lengthwise compaction, i.e., compaction of chromosomes along its contour, self-adhesion among epigenetically similar genomic segments, and adhesion of chromosome segments to the nuclear envelope or lamina. We postulate that these three types of interactions sufficiently represent the concerted action of the different proteins organizing the genome architecture and show that an interplay among these interactions can recapitulate the architectural variants observed across the tree of life. The model elucidates how an interplay of forces arising from the three classes of genomic interactions can drive drastic, yet predictable, changes in the global genome architecture, and makes testable predictions. We posit that precise control over these interactions in vivo is key to the regulation of genome architecture. |
format | Online Article Text |
id | pubmed-9071446 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-90714462022-05-06 Shaping the genome via lengthwise compaction, phase separation, and lamina adhesion Brahmachari, Sumitabha Contessoto, Vinícius G Di Pierro, Michele Onuchic, José N Nucleic Acids Res Computational Biology The link between genomic structure and biological function is yet to be consolidated, it is, however, clear that physical manipulation of the genome, driven by the activity of a variety of proteins, is a crucial step. To understand the consequences of the physical forces underlying genome organization, we build a coarse-grained polymer model of the genome, featuring three fundamentally distinct classes of interactions: lengthwise compaction, i.e., compaction of chromosomes along its contour, self-adhesion among epigenetically similar genomic segments, and adhesion of chromosome segments to the nuclear envelope or lamina. We postulate that these three types of interactions sufficiently represent the concerted action of the different proteins organizing the genome architecture and show that an interplay among these interactions can recapitulate the architectural variants observed across the tree of life. The model elucidates how an interplay of forces arising from the three classes of genomic interactions can drive drastic, yet predictable, changes in the global genome architecture, and makes testable predictions. We posit that precise control over these interactions in vivo is key to the regulation of genome architecture. Oxford University Press 2022-04-14 /pmc/articles/PMC9071446/ /pubmed/35420130 http://dx.doi.org/10.1093/nar/gkac231 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Computational Biology Brahmachari, Sumitabha Contessoto, Vinícius G Di Pierro, Michele Onuchic, José N Shaping the genome via lengthwise compaction, phase separation, and lamina adhesion |
title | Shaping the genome via lengthwise compaction, phase separation, and lamina adhesion |
title_full | Shaping the genome via lengthwise compaction, phase separation, and lamina adhesion |
title_fullStr | Shaping the genome via lengthwise compaction, phase separation, and lamina adhesion |
title_full_unstemmed | Shaping the genome via lengthwise compaction, phase separation, and lamina adhesion |
title_short | Shaping the genome via lengthwise compaction, phase separation, and lamina adhesion |
title_sort | shaping the genome via lengthwise compaction, phase separation, and lamina adhesion |
topic | Computational Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9071446/ https://www.ncbi.nlm.nih.gov/pubmed/35420130 http://dx.doi.org/10.1093/nar/gkac231 |
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