Transcription factor binding at Ig enhancers is linked to somatic hypermutation targeting
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F20%3A00559752" target="_blank" >RIV/68378050:_____/20:00559752 - isvavai.cz</a>
Result on the web
<a href="https://onlinelibrary.wiley.com/doi/10.1002/eji.201948357" target="_blank" >https://onlinelibrary.wiley.com/doi/10.1002/eji.201948357</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/eji.201948357" target="_blank" >10.1002/eji.201948357</a>
Alternative languages
Result language
angličtina
Original language name
Transcription factor binding at Ig enhancers is linked to somatic hypermutation targeting
Original language description
Secondary diversification of the Ig repertoire occurs through somatic hypermutation (SHM), gene conversion (GCV), and class switch recombination (CSR)-three processes that are initiated by activation-induced cytidine deaminase (AID). AID targets Ig genes at orders of magnitude higher than the rest of the genome, but the basis for this specificity is poorly understood. We have previously demonstrated that enhancers and enhancer-like sequences from Ig genes are capable of stimulating SHM of neighboring genes in a capacity distinct from their roles in increasing transcription. Here, we use an in vitro proteomics approach to identify E-box, MEF2, Ets, and Ikaros transcription factor family members as potential binders of these enhancers. ChIP assays in the hypermutating Ramos B cell line confirmed that many of these factors bound the endogenous Ig lambda enhancer and/or the IgH intronic enhancer (E mu) in vivo. Further investigation using SHM reporter assays identified binding sites for E2A and MEF2B in E mu and demonstrated an association between loss of factor binding and decreases in the SHM stimulating activity of E mu mutants. Our results provide novel insights into trans-acting factors that dictate SHM targeting and link their activity to specific DNA binding sites within Ig enhancers.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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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
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
European Journal of Immunology
ISSN
0014-2980
e-ISSN
1521-4141
Volume of the periodical
50
Issue of the periodical within the volume
3
Country of publishing house
DE - GERMANY
Number of pages
16
Pages from-to
380-395
UT code for WoS article
000503430500001
EID of the result in the Scopus database
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