Systematic assessment of gene co-regulation within chromatin domains determines differentially active domains across human cancers
Abstract Background Spatial interactions and insulation of chromatin regions are associated with transcriptional regulation. Domains of frequent chromatin contacts are proposed as functional units, favoring and delimiting gene regulatory interactions. However, contrasting evidence supports the assoc...
Main Authors: | , , , , |
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Format: | Article |
Language: | English |
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BMC
2021-08-01
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Series: | Genome Biology |
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Online Access: | https://doi.org/10.1186/s13059-021-02436-6 |
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author | Marie Zufferey Yuanlong Liu Daniele Tavernari Marco Mina Giovanni Ciriello |
author_facet | Marie Zufferey Yuanlong Liu Daniele Tavernari Marco Mina Giovanni Ciriello |
author_sort | Marie Zufferey |
collection | DOAJ |
description | Abstract Background Spatial interactions and insulation of chromatin regions are associated with transcriptional regulation. Domains of frequent chromatin contacts are proposed as functional units, favoring and delimiting gene regulatory interactions. However, contrasting evidence supports the association between chromatin domains and transcription. Result Here, we assess gene co-regulation in chromatin domains across multiple human cancers, which exhibit great transcriptional heterogeneity. Across all datasets, gene co-regulation is observed only within a small yet significant number of chromatin domains. We design an algorithmic approach to identify differentially active domains (DADo) between two conditions and show that these provide complementary information to differentially expressed genes. Domains comprising co-regulated genes are enriched in the less active B sub-compartments and for genes with similar function. Notably, differential activation of chromatin domains is not associated with major changes of domain boundaries, but rather with changes of sub-compartments and intra-domain contacts. Conclusion Overall, gene co-regulation is observed only in a minority of chromatin domains, whose systematic identification will help unravel the relationship between chromatin structure and transcription. |
first_indexed | 2024-12-13T21:49:56Z |
format | Article |
id | doaj.art-eb4e3a87952c4f1db806a5b0298be546 |
institution | Directory Open Access Journal |
issn | 1474-760X |
language | English |
last_indexed | 2024-12-13T21:49:56Z |
publishDate | 2021-08-01 |
publisher | BMC |
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series | Genome Biology |
spelling | doaj.art-eb4e3a87952c4f1db806a5b0298be5462022-12-21T23:30:18ZengBMCGenome Biology1474-760X2021-08-0122112410.1186/s13059-021-02436-6Systematic assessment of gene co-regulation within chromatin domains determines differentially active domains across human cancersMarie Zufferey0Yuanlong Liu1Daniele Tavernari2Marco Mina3Giovanni Ciriello4Department of Computational Biology, University of Lausanne (UNIL)Department of Computational Biology, University of Lausanne (UNIL)Department of Computational Biology, University of Lausanne (UNIL)Department of Computational Biology, University of Lausanne (UNIL)Department of Computational Biology, University of Lausanne (UNIL)Abstract Background Spatial interactions and insulation of chromatin regions are associated with transcriptional regulation. Domains of frequent chromatin contacts are proposed as functional units, favoring and delimiting gene regulatory interactions. However, contrasting evidence supports the association between chromatin domains and transcription. Result Here, we assess gene co-regulation in chromatin domains across multiple human cancers, which exhibit great transcriptional heterogeneity. Across all datasets, gene co-regulation is observed only within a small yet significant number of chromatin domains. We design an algorithmic approach to identify differentially active domains (DADo) between two conditions and show that these provide complementary information to differentially expressed genes. Domains comprising co-regulated genes are enriched in the less active B sub-compartments and for genes with similar function. Notably, differential activation of chromatin domains is not associated with major changes of domain boundaries, but rather with changes of sub-compartments and intra-domain contacts. Conclusion Overall, gene co-regulation is observed only in a minority of chromatin domains, whose systematic identification will help unravel the relationship between chromatin structure and transcription.https://doi.org/10.1186/s13059-021-02436-6Chromatin compartment domainsHi-CGene co-regulation |
spellingShingle | Marie Zufferey Yuanlong Liu Daniele Tavernari Marco Mina Giovanni Ciriello Systematic assessment of gene co-regulation within chromatin domains determines differentially active domains across human cancers Genome Biology Chromatin compartment domains Hi-C Gene co-regulation |
title | Systematic assessment of gene co-regulation within chromatin domains determines differentially active domains across human cancers |
title_full | Systematic assessment of gene co-regulation within chromatin domains determines differentially active domains across human cancers |
title_fullStr | Systematic assessment of gene co-regulation within chromatin domains determines differentially active domains across human cancers |
title_full_unstemmed | Systematic assessment of gene co-regulation within chromatin domains determines differentially active domains across human cancers |
title_short | Systematic assessment of gene co-regulation within chromatin domains determines differentially active domains across human cancers |
title_sort | systematic assessment of gene co regulation within chromatin domains determines differentially active domains across human cancers |
topic | Chromatin compartment domains Hi-C Gene co-regulation |
url | https://doi.org/10.1186/s13059-021-02436-6 |
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