Topologically Associated Domains Delineate Susceptibility to Somatic Hypermutation

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dc.citation.firstpage3902
dc.citation.issueNumber12
dc.citation.journalTitleCell Reports
dc.citation.lastpage3915.e8
dc.citation.volumeNumber29
dc.contributor.authorSenigl, Filip
dc.contributor.authorMaman, Yaakov
dc.contributor.authorDinesh, Ravi K.
dc.contributor.authorAlinikula, Jukka
dc.contributor.authorSeth, Rashu B.
dc.contributor.authorPecnova, Lubomira
dc.contributor.authorOmer, Arina D.
dc.contributor.authorRao, Suhas S. P.
dc.contributor.authorWeisz, David
dc.contributor.authorBuerstedde, Jean-Marie
dc.contributor.authorAiden, Erez Lieberman
dc.contributor.authorCasellas, Rafael
dc.contributor.authorHejnar, Jiri
dc.contributor.authorSchatz, David G.
dc.contributor.orgCenter for Theoretical Biological Physics
dc.date.accessioned2021-10-06T14:15:18Z
dc.date.available2021-10-06T14:15:18Z
dc.date.issued2019
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.
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.
dc.identifier.digital1-s2-0-S2211124719315219-main
dc.identifier.doihttps://doi.org/10.1016/j.celrep.2019.11.039
dc.identifier.urihttps://hdl.handle.net/1911/111439
dc.language.isoeng
dc.publisherElsevier
dc.rightsThis is an open access article under the Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleTopologically Associated Domains Delineate Susceptibility to Somatic Hypermutation
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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