Evidence map›Paper›PMID 31821534›Full record

ArticleEuropean journal of immunology2020

Transcription factor binding at Ig enhancers is linked to somatic hypermutation targeting.

Ravi K Dinesh, Benjamin Barnhill, Anoj Ilanges, Lizhen Wu, Daniel A Michelson, Filip Senigl, Jukka Alinikula, Jeffrey Shabanowitz, Donald F Hunt, David G Schatz

Open access · bronzeAbstract read
In one paragraph

Article in European journal of immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.0field-weighted citation impact, top 24% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Promoter Proximity Defines Mutation Window for VJournal of immunology (Baltimore, Md. : 1950) · 2022
    Article
  9. Article
  10. Review
  11. Article
  12. The role of HIRA-dependent H3.3 deposition and its modifications in the somatic hypermutation of immunoglobulin variable regions.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  13. Article
  14. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 4 countries.

Ravi K DineshDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
Benjamin BarnhillDepartment of Chemistry, University of Virginia, Charlottesville, VA, USA.
Anoj IlangesDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
Lizhen WuDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
Daniel A MichelsonDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
Filip SeniglInstitute of Molecular Genetics, Czech Academy of Sciences, Videnska 1083, CZ-14220, Prague 4, Czech Republic.
Jukka AlinikulaInstitute of Biomedicine, University of Turku, Turku, Finland.
Jeffrey ShabanowitzDepartment of Chemistry, University of Virginia, Charlottesville, VA, USA.
Donald F HuntDepartment of Chemistry, University of Virginia, Charlottesville, VA, USA.
David G SchatzDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.ORCID 0000-0002-5669-1176
Yale University · USUniversity of Virginia · USCzech Academy of Sciences · CZUniversity of Turku · FI

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
PROTEIN SEQUENCING BY TANDEM MASS SPECTROMETRYR01GM037537 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI HUNT, DONALD F · 1987 to 2023
$17.8M
Targeting of somatic hypermutation in the genomeR01AI127642 · NIAID · YALE UNIVERSITY · PI SCHATZ, DAVID G. · 2017 to 2025
$4.6M
Cancer Society of South-West FinlandElla and Georg Ehrnrooth FoundationEmil Aaltonen FoundationGrantová Agentura České Republiky 15-24776SJane and Aatos Erkko FoundationJenny and Antti Wihuri FoundationNCATS NIH HHS UL1 TR001863NIAID NIH HHS R01 AI127642NIGMS NIH HHS R01 GM037537Sigrid Juselius Foundation
6 · The paper itself

Abstract

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 Igλ enhancer and/or the IgH intronic enhancer (Eμ) in vivo. Further investigation using SHM reporter assays identified binding sites for E2A and MEF2B in Eμ and demonstrated an association between loss of factor binding and decreases in the SHM stimulating activity of Eμ 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.

Indexed as

AnimalsChickensGenes, ImmunoglobulinHumansSomatic Hypermutation, ImmunoglobulinTranscription FactorsTranscription FactorsAIDE2AMEF2BRamos B cell lineSomatic hypermutation

Identifiers

PMID31821534
PMCPMC7202714
OpenAlexW2996468895

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.