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A pathway-centric view of spatial proximity in the 3D nucleome across cell lines

In various contexts, spatially proximal genes have been shown to be functionally related. However, the extent to which spatial proximity of genes in a pathway contributes to the pathway’s context-specific activity is not known. Leveraging Hi-C data in six human cell-lines, we show that spatial proxi...

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Detalles Bibliográficos
Autores principales: Karathia, Hiren, Kingsford, Carl, Girvan, Michelle, Hannenhalli, Sridhar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5157015/
https://www.ncbi.nlm.nih.gov/pubmed/27976707
http://dx.doi.org/10.1038/srep39279
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author Karathia, Hiren
Kingsford, Carl
Girvan, Michelle
Hannenhalli, Sridhar
author_facet Karathia, Hiren
Kingsford, Carl
Girvan, Michelle
Hannenhalli, Sridhar
author_sort Karathia, Hiren
collection PubMed
description In various contexts, spatially proximal genes have been shown to be functionally related. However, the extent to which spatial proximity of genes in a pathway contributes to the pathway’s context-specific activity is not known. Leveraging Hi-C data in six human cell-lines, we show that spatial proximity of genes in a pathway is highly correlated with the pathway’s context-specific expression and function. Furthermore, spatial proximity of pathway genes correlates with interactions of their protein products, and the specific pathway genes that are proximal to one another tend to occupy higher levels in the regulatory hierarchy. In addition to intra-pathway proximity, related pathways are spatially proximal to one another and housekeeping-genes tend to be proximal to several other pathways suggesting their coordinating role. Substantially extending previous works, our study reveals a pathway-centric organization of 3D-nucleome, whereby, functionally related interacting driver genes tend to be in spatial-proximity in a context-specific manner.
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spelling pubmed-51570152016-12-20 A pathway-centric view of spatial proximity in the 3D nucleome across cell lines Karathia, Hiren Kingsford, Carl Girvan, Michelle Hannenhalli, Sridhar Sci Rep Article In various contexts, spatially proximal genes have been shown to be functionally related. However, the extent to which spatial proximity of genes in a pathway contributes to the pathway’s context-specific activity is not known. Leveraging Hi-C data in six human cell-lines, we show that spatial proximity of genes in a pathway is highly correlated with the pathway’s context-specific expression and function. Furthermore, spatial proximity of pathway genes correlates with interactions of their protein products, and the specific pathway genes that are proximal to one another tend to occupy higher levels in the regulatory hierarchy. In addition to intra-pathway proximity, related pathways are spatially proximal to one another and housekeeping-genes tend to be proximal to several other pathways suggesting their coordinating role. Substantially extending previous works, our study reveals a pathway-centric organization of 3D-nucleome, whereby, functionally related interacting driver genes tend to be in spatial-proximity in a context-specific manner. Nature Publishing Group 2016-12-15 /pmc/articles/PMC5157015/ /pubmed/27976707 http://dx.doi.org/10.1038/srep39279 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Karathia, Hiren
Kingsford, Carl
Girvan, Michelle
Hannenhalli, Sridhar
A pathway-centric view of spatial proximity in the 3D nucleome across cell lines
title A pathway-centric view of spatial proximity in the 3D nucleome across cell lines
title_full A pathway-centric view of spatial proximity in the 3D nucleome across cell lines
title_fullStr A pathway-centric view of spatial proximity in the 3D nucleome across cell lines
title_full_unstemmed A pathway-centric view of spatial proximity in the 3D nucleome across cell lines
title_short A pathway-centric view of spatial proximity in the 3D nucleome across cell lines
title_sort pathway-centric view of spatial proximity in the 3d nucleome across cell lines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5157015/
https://www.ncbi.nlm.nih.gov/pubmed/27976707
http://dx.doi.org/10.1038/srep39279
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