Evidence map›Paper›PMID 34862258›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2022

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

Alina Tarsalainen, Yaakov Maman, Fei-Long Meng, Minna K Kyläniemi, Anni Soikkeli, Paulina Budzyńska, Jessica J McDonald, Filip Šenigl, Frederic W Alt, David G Schatz and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

13 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
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  7. Review
  8. Article
  9. Evolutionary analysis of a complete chicken genome.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  10. Article
  11. The IgHFrontiers in immunology · 2023
    Article
  12. Article
  13. 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

11 authors at 5 institutions in 5 countries.

Alina TarsalainenUnit of Infections and Immunity, Institute of Biomedicine, University of Turku, Turku, Finland.ORCID 0000-0002-7155-5316
Yaakov MamanThe Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel.
Fei-Long MengHoward Hughes Medical Institute, Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA.
Minna K KyläniemiUnit of Infections and Immunity, Institute of Biomedicine, University of Turku, Turku, Finland.ORCID 0000-0001-7374-9862
Anni SoikkeliUnit of Infections and Immunity, Institute of Biomedicine, University of Turku, Turku, Finland.
Paulina BudzyńskaUnit of Infections and Immunity, Institute of Biomedicine, University of Turku, Turku, Finland.ORCID 0000-0002-2896-6806
Jessica J McDonaldDepartment of Immunobiology, Yale School of Medicine, New Haven, CT; and.ORCID 0000-0002-5897-8947
Filip ŠeniglInstitute of Molecular Genetics, Academy of Sciences of the Czech Republic, Praha, Czech Republic.
Frederic W AltHoward Hughes Medical Institute, Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA.ORCID 0000-0002-0583-1271
David G SchatzDepartment of Immunobiology, Yale School of Medicine, New Haven, CT; and david.schatz@yale.edu jukka.alinikula@utu.fi.ORCID 0000-0002-5669-1176
Jukka AlinikulaUnit of Infections and Immunity, Institute of Biomedicine, University of Turku, Turku, Finland; david.schatz@yale.edu jukka.alinikula@utu.fi.ORCID 0000-0001-9926-6439
University of Turku · FIBoston Children's Hospital · USYale University · USBar-Ilan University · ILInstitute of Molecular Genetics · RU

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
INTERDISCIPLINARY IMMUNOLOGY TRAINING PROGRAMT32AI007019 · NIAID · YALE UNIVERSITY · PI Carrie L. Lucas, David G. Schatz · 1985 to 2026
$14.4M
Targeting of somatic hypermutation in the genomeR01AI127642 · NIAID · YALE UNIVERSITY · PI SCHATZ, DAVID G. · 2017 to 2025
$4.6M
NCATS NIH HHS UL1 TR001863NIAID NIH HHS R01 AI127642NIAID NIH HHS T32 AI007019
6 · The paper itself

Abstract

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

Indexed as

AICDA (Activation-Induced Cytidine Deaminase)AnimalsAntibody DiversityAvian ProteinsB-Lymphocyte SubsetsBurkitt LymphomaChickensCytidine DeaminaseEnhancer Elements, GeneticHumansImmunoglobulinsLymphocyte ActivationMutagenesis, Site-DirectedMutationRNA Polymerase IISomatic Hypermutation, ImmunoglobulinAICDA (Activation-Induced Cytidine Deaminase)Avian ProteinsCytidine DeaminaseImmunoglobulinsRNA Polymerase II

Identifiers

PMID34862258
PMCPMC8702490
OpenAlexW3217736816

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.