Ig Enhancers Increase RNA Polymerase II Stalling at Somatic Hypermutation Target Sequences

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F22%3A00555983" target="_blank" >RIV/68378050:_____/22:00555983 - isvavai.cz</a>

Result on the web

<a href="https://journals.aai.org/jimmunol/article/208/1/143/234155/Ig-Enhancers-Increase-RNA-Polymerase-II-Stalling" target="_blank" >https://journals.aai.org/jimmunol/article/208/1/143/234155/Ig-Enhancers-Increase-RNA-Polymerase-II-Stalling</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.4049/jimmunol.2100923" target="_blank" >10.4049/jimmunol.2100923</a>

Result language

angličtina

Original language name

Ig Enhancers Increase RNA Polymerase II Stalling at Somatic Hypermutation Target Sequences

Original language description

Somatic hypermutation (SHM) drives the genetic diversity of Ig genes in activated B cells and supports the generation of Abs with increased affinity for Ag. SHM is targeted to Ig genes by their enhancers (diversification activators [DIVACs]), but how the enhancers mediate this activity is unknown. We show using chicken DT40 B cells that highly active DIVACs increase the phosphorylation of RNA polymerase II (Pol II) and Pol II occupancy in the mutating gene with little or no accompanying increase in elongation competent Pol II or production of full-length transcripts, indicating accumulation of stalled Pol II. DIVAC has similar effect also in human Ramos Burkitt lymphoma cells. The DIVAC-induced stalling is weakly associated with an increase in the detection of ssDNA bubbles in the mutating target gene. We did not find evidence for antisense transcription, or that DIVAC functions by altering levels of H3K27ac or the histone variant H3.3 in the mutating gene. These findings argue for a connection between Pol II stalling and cis acting targeting elements in the context of SHM and thus define a mechanistic basis for locus-specific targeting of SHM in the genome. Our results suggest that DIVAC elements render the target gene a suitable platform for AID-mediated mutation without a requirement for increasing transcriptional output.

Czech name

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Czech description

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Type

J_imp - 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

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

Publication year

2022

Confidentiality

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

Name of the periodical

Journal of Immunology

ISSN

0022-1767

e-ISSN

1550-6606

Volume of the periodical

208

Issue of the periodical within the volume

1

Country of publishing house

US - UNITED STATES

Number of pages

12

Pages from-to

143-154

UT code for WoS article

000735220200015

EID of the result in the Scopus database

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