Topologically Associated Domains Delineate Susceptibility to Somatic Hypermutation

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dc.citation.firstpage3902en_US
dc.citation.issueNumber12en_US
dc.citation.journalTitleCell Reportsen_US
dc.citation.lastpage3915.e8en_US
dc.citation.volumeNumber29en_US
dc.contributor.authorSenigl, Filipen_US
dc.contributor.authorMaman, Yaakoven_US
dc.contributor.authorDinesh, Ravi K.en_US
dc.contributor.authorAlinikula, Jukkaen_US
dc.contributor.authorSeth, Rashu B.en_US
dc.contributor.authorPecnova, Lubomiraen_US
dc.contributor.authorOmer, Arina D.en_US
dc.contributor.authorRao, Suhas S. P.en_US
dc.contributor.authorWeisz, Daviden_US
dc.contributor.authorBuerstedde, Jean-Marieen_US
dc.contributor.authorAiden, Erez Liebermanen_US
dc.contributor.authorCasellas, Rafaelen_US
dc.contributor.authorHejnar, Jirien_US
dc.contributor.authorSchatz, David G.en_US
dc.contributor.orgCenter for Theoretical Biological Physicsen_US
dc.date.accessioned2021-10-06T14:15:18Zen_US
dc.date.available2021-10-06T14:15:18Zen_US
dc.date.issued2019en_US
dc.description.abstractSomatic hypermutation (SHM) introduces point mutations into immunoglobulin (Ig) genes but also causes mutations in other parts of the genome. We have used lentiviral SHM reporter vectors to identify regions of the genome that are susceptible (“hot”) and resistant (“cold”) to SHM, revealing that SHM susceptibility and resistance are often properties of entire topologically associated domains (TADs). Comparison of hot and cold TADs reveals that while levels of transcription are equivalent, hot TADs are enriched for the cohesin loader NIPBL, super-enhancers, markers of paused/stalled RNA polymerase 2, and multiple important B cell transcription factors. We demonstrate that at least some hot TADs contain enhancers that possess SHM targeting activity and that insertion of a strong Ig SHM-targeting element into a cold TAD renders it hot. Our findings lead to a model for SHM susceptibility involving the cooperative action of cis-acting SHM targeting elements and the dynamic and architectural properties of TADs.en_US
dc.identifier.citationSenigl, Filip, Maman, Yaakov, Dinesh, Ravi K., et al.. "Topologically Associated Domains Delineate Susceptibility to Somatic Hypermutation." <i>Cell Reports,</i> 29, no. 12 (2019) Elsevier: 3902-3915.e8. https://doi.org/10.1016/j.celrep.2019.11.039.en_US
dc.identifier.digital1-s2-0-S2211124719315219-mainen_US
dc.identifier.doihttps://doi.org/10.1016/j.celrep.2019.11.039en_US
dc.identifier.urihttps://hdl.handle.net/1911/111439en_US
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.rightsThis is an open access article under the Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) licenseen_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.titleTopologically Associated Domains Delineate Susceptibility to Somatic Hypermutationen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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