A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Topologically Associated Domains Delineate Susceptibility to Somatic Hypermutation
Tekijät: Senigl F, Maman Y, Dinesh RK, Alinikula J, Seth RB, Pecnova L, Omer AD, Rao SSP, Weisz D, Buerstedde JM, Aiden EL, Casellas R, Hejnar J, Schatz DG
Kustantaja: CELL PRESS
Julkaisuvuosi: 2019
Journal: Cell Reports
Tietokannassa oleva lehden nimi: CELL REPORTS
Lehden akronyymi: CELL REP
Vuosikerta: 29
Numero: 12
Aloitussivu: 3902
Lopetussivu: 3915.e8
Sivujen määrä: 22
ISSN: 2211-1247
DOI: https://doi.org/10.1016/j.celrep.2019.11.039
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/44068895
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.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
