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...

Full description

Bibliographic Details
Main Authors: Marie Zufferey, Yuanlong Liu, Daniele Tavernari, Marco Mina, Giovanni Ciriello
Format: Article
Language:English
Published: BMC 2021-08-01
Series:Genome Biology
Subjects:
Online Access:https://doi.org/10.1186/s13059-021-02436-6
_version_ 1818363529651027968
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
record_format Article
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
work_keys_str_mv AT mariezufferey systematicassessmentofgenecoregulationwithinchromatindomainsdeterminesdifferentiallyactivedomainsacrosshumancancers
AT yuanlongliu systematicassessmentofgenecoregulationwithinchromatindomainsdeterminesdifferentiallyactivedomainsacrosshumancancers
AT danieletavernari systematicassessmentofgenecoregulationwithinchromatindomainsdeterminesdifferentiallyactivedomainsacrosshumancancers
AT marcomina systematicassessmentofgenecoregulationwithinchromatindomainsdeterminesdifferentiallyactivedomainsacrosshumancancers
AT giovanniciriello systematicassessmentofgenecoregulationwithinchromatindomainsdeterminesdifferentiallyactivedomainsacrosshumancancers