Number of the records: 1  

Topologically Associated Domains Delineate Susceptibility to Somatic Hypermutation

  1. 1.
    0520645 - ÚMG 2020 RIV US eng J - Journal Article
    Šenigl, Filip - Maman, Y. - Dinesh, R. K. - Alinikula, J. - Seth, R. B. - Pecnová, Lubomíra - Omer, A. D. - Rao, S. S. P. - Weisz, D. - Buerstedde, J.-M. - Aiden, E. L. - Casellas, R. - Hejnar, Jiří - Schatz, D. G.
    Topologically Associated Domains Delineate Susceptibility to Somatic Hypermutation.
    Cell Reports. Roč. 29, č. 12 (2019), s. 3902-3915. ISSN 2211-1247. E-ISSN 2211-1247
    R&D Projects: GA ČR GA15-24776S
    Institutional support: RVO:68378050
    Keywords : center b-cells * super-enhancers * targets aid * molecular-mechanisms * human genome * dna * gene * translocations * transcription * integration
    OECD category: Immunology
    Impact factor: 8.109, year: 2019
    Method of publishing: Open access
    https://www.cell.com/cell-reports/fulltext/S2211-1247(19)31521-9?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124719315219%3Fshowall%3Dtrue

    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.
    Permanent Link: http://hdl.handle.net/11104/0305794

     
    FileDownloadSizeCommentaryVersionAccess
    Cell_Reports_F_Senigl_2019.pdf14.6 MBPublisher’s postprintrequire
     
Number of the records: 1  

  This site uses cookies to make them easier to browse. Learn more about how we use cookies.