Evidence map›Paper›PMID 24218622›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2013

Peripheral subnuclear positioning suppresses Tcrb recombination and segregates Tcrb alleles from RAG2.

Elizabeth A W Chan, Grace Teng, Elizabeth Corbett, Kingshuk Roy Choudhury, Craig H Bassing, David G Schatz, Michael S Krangel

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

18 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Nucleolar localization of RAG1 modulates V(D)J recombination activity.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  8. Article
  9. Article
  10. Article
  11. Immature Lymphocytes InhibitJournal of immunology (Baltimore, Md. : 1950) · 2017
    Article
  12. Article
  13. Assembly and Expression of Shark Ig Genes.Journal of immunology (Baltimore, Md. : 1950) · 2016
    Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. E proteins in lymphocyte development and lymphoid diseases.Current topics in developmental biology · 2014
    Review
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

7 authors at 3 institutions in 1 country.

Elizabeth A W ChanDepartments of Immunology, Radiology, and Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC 27710.
Grace Teng
Elizabeth Corbett
Kingshuk Roy Choudhury
Craig H Bassing
David G Schatz
Michael S Krangel
Children's Hospital of Philadelphia · USDuke University · USYale University · US

Funding

CONTROL OF TCR V BETA REARRANGEMENT &ALLELIC EXCLUSIONR01AI049934 · NIAID · DUKE UNIVERSITY · PI KRANGEL, MICHAEL S · 2001 to 2015
$6.8M
Immunoglobulin and T Cell Receptor Gene AssemblyR37AI032524 · NIAID · YALE UNIVERSITY · PI SCHATZ, DAVID G. · 2007 to 2016
$3.5M
Innovative therapy for diseases of the middle earR01DC012595 · NIDCD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI RYAN, ALLEN F. · 2012 to 2023
$3.3M
NCI NIH HHS R01 CA12595NIAID NIH HHS R01 AI049934NIAID NIH HHS R01 AI49934NIAID NIH HHS R37 AI032524NIAID NIH HHS R37 AI32524NIDCD NIH HHS R01 DC012595
6 · The paper itself

Abstract

Allelic exclusion requires that the two alleles at antigen-receptor loci attempt to recombine variable (V), diversity (D), and joining (J) gene segments [V(D)J recombination] asynchronously in nuclei of developing lymphocytes. It previously was shown that T-cell receptor β (Tcrb) alleles frequently and stochastically associate with the nuclear lamina and pericentromeric heterochromatin in CD4(-)CD8(-) thymocytes. Moreover, rearranged alleles were underrepresented at these locations. Here we used 3D immunofluorescence in situ hybridization to identify recently rearranged Tcrb alleles based on the accumulation of the DNA-repair protein 53BP1. We found that Tcrb alleles recombine asynchronously in double-negative thymocytes and that V(D)J recombination is suppressed on peripheral as compared with central Tcrb alleles. Moreover, the recombination events that did take place at the nuclear periphery preferentially occurred on Tcrb alleles that were partially dissociated from the nuclear lamina. To understand better the mechanism by which V(D)J recombination is suppressed at the nuclear periphery, we evaluated the subnuclear distribution of recombination-activating gene 2 (RAG2) protein. We found that RAG2 abundance was reduced at the nuclear periphery. Moreover, RAG2 was distributed differently from RNA polymerase II and histone H3K4 trimethylation. Our data suggest that the nuclear periphery suppresses V(D)J recombination, at least in part, by segregating Tcrb alleles from RAG proteins.

Indexed as

AnimalsCell NucleusDNA-Binding ProteinsImage Processing, Computer-AssistedIn Situ Hybridization, FluorescenceMiceMice, KnockoutMicroscopy, ConfocalReceptors, Antigen, T-Cell, alpha-betaRecombination, GeneticDNA-Binding ProteinsRag2 protein, mouseReceptors, Antigen, T-Cell, alpha-betaT-cell developmentthymus

Identifiers

PMID24218622
PMCPMC3845165
OpenAlexW2061194533

What OpenQuestion holds

Textmetadata
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.