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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...

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Autores principales: Brahmachari, Sumitabha, Contessoto, Vinícius G, Di Pierro, Michele, Onuchic, José N
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
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.
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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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