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Topologically Associated Domains Delineate Susceptibility to Somatic Hypermutation

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F19%3A00520645" target="_blank" >RIV/68378050:_____/19:00520645 - isvavai.cz</a>

  • Result on the web

    <a href="https://www.cell.com/cell-reports/fulltext/S2211-1247(19)31521-9?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124719315219%3Fshowall%3Dtrue" target="_blank" >https://www.cell.com/cell-reports/fulltext/S2211-1247(19)31521-9?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124719315219%3Fshowall%3Dtrue</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1016/j.celrep.2019.11.039" target="_blank" >10.1016/j.celrep.2019.11.039</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Topologically Associated Domains Delineate Susceptibility to Somatic Hypermutation

  • Original language description

    Somatic 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.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    30102 - Immunology

Result continuities

  • Project

    <a href="/en/project/GA15-24776S" target="_blank" >GA15-24776S: Mistargeting of somatic hypermutation and its role in B cell genome instability</a><br>

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2019

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Cell Reports

  • ISSN

    2211-1247

  • e-ISSN

  • Volume of the periodical

    29

  • Issue of the periodical within the volume

    12

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    14

  • Pages from-to

    3902-3915

  • UT code for WoS article

    000503201800013

  • EID of the result in the Scopus database