Topologically Associated Domains Delineate Susceptibility to Somatic Hypermutation

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Topologically Associated Domains Delineate Susceptibility to Somatic Hypermutation

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Topologically Associated Domains Delineate Susceptibility to Somatic Hypermutation

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30102 - Immunology

Projekt

<a href="/cs/project/GA15-24776S" target="_blank" >GA15-24776S: Chybné cílení somatických hypermutací a jeho vliv na nestabilitu genomu B lymfocytů</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

Cell Reports

ISSN

2211-1247

e-ISSN

—

Svazek periodika

29

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

14

Strana od-do

3902-3915

Kód UT WoS článku

000503201800013

EID výsledku v databázi Scopus

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