Evidence map›Paper›PMID 40833849›Full record

ArticleCell reports2025

Promoter- and enhancer-dependent cohesin loading initiates chromosome looping to fold Tcrb loci for long-range recombination.

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

Abstract read
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

8 authors.

Brittney M AllynImmunology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Katharina E HayerDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Biomedical Engineering Doctoral Degree Program, School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA 19104, USA; Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Perelman School of Medicine, Philadelphia, PA 19104, USA.
Clement OyeniranDepartment of Microbial Infection and Immunity, Ohio State College of Medicine, Ohio State University, Columbus, OH 43210, USA.
Vincent NgangaDepartment of Microbial Infection and Immunity, Ohio State College of Medicine, Ohio State University, Columbus, OH 43210, USA.
Kyutae LeeDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Ahmet SacanBiomedical Engineering Doctoral Degree Program, School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA 19104, USA.
Eugene M OltzDepartment of Microbial Infection and Immunity, Ohio State College of Medicine, Ohio State University, Columbus, OH 43210, USA; Pelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH 43210, USA. Electronic address: eugene.oltz@osumc.edu.
Craig H BassingImmunology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: bassing@chop.edu.

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
Elucidating Mechanisms of RAG Endonuclease Mediated Feedback Inhibition of V(D)J RecombinationR01AI172163 · NIAID · CHILDREN'S HOSP OF PHILADELPHIA · PI BASSING, CRAIG H · 2022 to 2025
$2.2M
TOPOLOGICAL MECHANISMS OF DNA BREAK REPAIR IN LYMPHOCYTESR01AI118852 · NIAID · WASHINGTON UNIVERSITY · PI OLTZ, EUGENE M · 2015 to 2019
$1.9M
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 AI118852NIAID NIH HHS R01 AI130231NIAID NIH HHS R01 AI172163NIAID NIH HHS R21 AI174545NIAID NIH HHS R37 AI118852
6 · The paper itself

Abstract

Cohesin-mediated chromosome looping regulates diverse processes, including antigen receptor (AgR) gene assembly by V(D)J recombination. To understand the mechanisms that coordinate genome topologies, we focused on a genetically tractable AgR locus, Tcrb. Cohesin loading and initiation of loop extrusion (LE) from a nearby CTCF-binding element (CBE) required the promoter of the most 5'Vb segment, creating long-range contacts with downstream DJb segments in the recombination center (RC). CBEs flanking the RC have multiple functions: termination of LE originating in the Vb cluster, initiation of LE in the RC, and insulation of enhancer activity. Deletion of the Tcrb super-enhancer abolished LE from the neighboring RC but spared long-range contacts, indicating that unidirectional LE from upstream Vb segments was sufficient. Thus, Vb promoter- or enhancer-dependent cohesin loading initiates LE in opposite directions across the locus to assemble a broad Tcrb repertoire, a finding that has broad implications for genomic architecture and function.

Indexed as

Cell Cycle ProteinsChromosomal Proteins, Non-HistoneEnhancer Elements, GeneticPromoter Regions, GeneticReceptors, Antigen, T-Cell, alpha-betaAnimalsCCCTC-Binding FactorCohesinsMiceV(D)J RecombinationCCCTC-Binding FactorCell Cycle ProteinsChromosomal Proteins, Non-HistoneCohesinsReceptors, Antigen, T-Cell, alpha-betachromosome loopingcohesin-mediated loop extrusionCP: Molecular biologygenome topologyV(D)J recombination

Identifiers

PMID40833849
PMCPMC12860192

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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.