Somatic structural variant formation is guided by and influences genome architecture

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dc.citation.firstpage643en_US
dc.citation.journalTitleGenome Researchen_US
dc.citation.lastpage655en_US
dc.citation.volumeNumber32en_US
dc.contributor.authorSidiropoulos, Nikosen_US
dc.contributor.authorMardin, Balca R.en_US
dc.contributor.authorRodríguez-González, F. Germánen_US
dc.contributor.authorBochkov, Ivan D.en_US
dc.contributor.authorGarg, Shilpaen_US
dc.contributor.authorStütz, Adrian M.en_US
dc.contributor.authorKorbel, Jan O.en_US
dc.contributor.authorAiden, Erez Liebermanen_US
dc.contributor.authorWeischenfeldt, Joachimen_US
dc.contributor.orgCenter for Theoretical Biological Physicsen_US
dc.date.accessioned2022-04-28T14:28:57Zen_US
dc.date.available2022-04-28T14:28:57Zen_US
dc.date.issued2022en_US
dc.description.abstractThe occurrence and formation of genomic structural variants (SVs) is known to be influenced by the 3D chromatin architecture, but the extent and magnitude have been challenging to study. Here, we apply Hi-C to study chromatin organization before and after induction of chromothripsis in human cells. We use Hi-C to manually assemble the derivative chromosomes following the occurrence of massive complex rearrangements, which allows us to study the sources of SV formation and their consequences on gene regulation. We observe an action–reaction interplay whereby the 3D chromatin architecture directly impacts the location and formation of SVs. In turn, the SVs reshape the chromatin organization to alter the local topologies, replication timing, and gene regulation in cis. We show that SVs have a strong tendency to occur between similar chromatin compartments and replication timing regions. Moreover, we find that SVs frequently occur at 3D loop anchors, that SVs can cause a switch in chromatin compartments and replication timing, and that this is a major source of SV-mediated effects on nearby gene expression changes. Finally, we provide evidence for a general mechanistic bias of the 3D chromatin on SV occurrence using data from more than 2700 patient-derived cancer genomes.en_US
dc.identifier.citationSidiropoulos, Nikos, Mardin, Balca R., Rodríguez-González, F. Germán, et al.. "Somatic structural variant formation is guided by and influences genome architecture." <i>Genome Research,</i> 32, (2022) Cold Spring Harbor Laboratory Press: 643-655. https://doi.org/10.1101/gr.275790.121.en_US
dc.identifier.digitalSidiropoulos-643-55en_US
dc.identifier.doihttps://doi.org/10.1101/gr.275790.121en_US
dc.identifier.urihttps://hdl.handle.net/1911/112178en_US
dc.language.isoengen_US
dc.publisherCold Spring Harbor Laboratory Pressen_US
dc.rightsThis article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.en_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/.en_US
dc.titleSomatic structural variant formation is guided by and influences genome architectureen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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