Evidence map›Paper›PMID 38189780›Full record

ArticleThe Journal of experimental medicine2024

Locus folding mechanisms determine modes of antigen receptor gene assembly.

Brittney M Allyn, Katharina E Hayer, Clement Oyeniran, Vincent Nganga, Kyutae Lee, Bikash Mishra, Ahmet Sacan, Eugene M Oltz, Craig H Bassing

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

6 citing papers in PubMed, 10 citations in OpenAlex.

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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

9 authors at 3 institutions in 1 country.

Brittney M AllynImmunology Graduate Group, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA, USA.ORCID 0000-0003-1254-6097
Katharina E HayerDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-1463-3111
Clement OyeniranDepartment of Microbial Infection and Immunity, Ohio State College of Medicine, Ohio State University, Columbus, OH, USA.ORCID 0000-0002-6777-425X
Vincent NgangaDepartment of Microbial Infection and Immunity, Ohio State College of Medicine, Ohio State University, Columbus, OH, USA.ORCID 0000-0003-0879-6560
Kyutae LeeDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-0348-8019
Bikash MishraDepartment of Microbial Infection and Immunity, Ohio State College of Medicine, Ohio State University, Columbus, OH, USA.ORCID 0000-0002-7351-2096
Ahmet SacanBiomedical Engineering Doctoral Degree Program, School of Biomedical Engineering, Science and Health Systems, Drexel University , Philadelphia, PA, USA.ORCID 0000-0002-3570-3270
Eugene M OltzDepartment of Microbial Infection and Immunity, Ohio State College of Medicine, Ohio State University, Columbus, OH, USA.ORCID 0000-0002-2513-7156
Craig H BassingImmunology Graduate Group, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA, USA.ORCID 0000-0003-1703-0786
Children's Hospital of Philadelphia · USThe Ohio State University · USDrexel University · US

Funding

Topological Control of Antigen Receptor Loci during Lymphocyte DevelopmentR01AI130231 · NIAID · CHILDREN'S HOSP OF PHILADELPHIA · PI BASSING, CRAIG H, OLTZ, EUGENE M · 2017 to 2021
$3.8M
TOPOLOGICAL MECHANISMS OF DNA BREAK REPAIR IN LYMPHOCYTESR37AI118852 · NIAID · OHIO STATE UNIVERSITY · PI Eugene M Oltz · 2021 to 2026
$2.8M
Exploring a Functional Role of Chromosome Loop Extrusion Direction on Regulating Genome BiologyR21AI174545 · NIAID · CHILDREN'S HOSP OF PHILADELPHIA · PI BASSING, CRAIG H · 2023 to 2024
$490k
NIAID NIH HHS R01 AI130231NIAID NIH HHS R21 AI174545NIAID NIH HHS R37 AI118852NIH HHS R01 AI130231
6 · The paper itself

Abstract

The dynamic folding of genomes regulates numerous biological processes, including antigen receptor (AgR) gene assembly. We show that, unlike other AgR loci, homotypic chromatin interactions and bidirectional chromosome looping both contribute to structuring Tcrb for efficient long-range V(D)J recombination. Inactivation of the CTCF binding element (CBE) or promoter at the most 5'Vβ segment (Trbv1) impaired loop extrusion originating locally and extending to DβJβ CBEs at the opposite end of Tcrb. Promoter or CBE mutation nearly eliminated Trbv1 contacts and decreased RAG endonuclease-mediated Trbv1 recombination. Importantly, Trbv1 rearrangement can proceed independent of substrate orientation, ruling out scanning by DβJβ-bound RAG as the sole mechanism of Vβ recombination, distinguishing it from Igh. Our data indicate that CBE-dependent generation of loops cooperates with promoter-mediated activation of chromatin to juxtapose Vβ and DβJβ segments for recombination through diffusion-based synapsis. Thus, the mechanisms that fold a genomic region can influence molecular processes occurring in that space, which may include recombination, repair, and transcriptional programming.

Indexed as

ChromatinReceptors, AntigenEndonucleasesMutationPromoter Regions, GeneticReceptors, Antigen, T-Cell, alpha-betaChromatinEndonucleasesReceptors, AntigenReceptors, Antigen, T-Cell, alpha-beta

Identifiers

PMID38189780
PMCPMC10772921
OpenAlexW4390673419

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.