Evidence map›Paper›PMID 25543141›Full record

ArticleCell reports2015

An autoregulatory mechanism imposes allosteric control on the V(D)J recombinase by histone H3 methylation.

Chao Lu, Alyssa Ward, John Bettridge, Yun Liu, Stephen Desiderio

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

20 citing papers in PubMed, 45 citations in OpenAlex.

  1. Article
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  5. Review
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  10. Review
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  12. Review
  13. Article
  14. Article
  15. H3K4me3 induces allosteric conformational changes in the DNA-binding and catalytic regions of the V(D)J recombinase.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  16. Review
  17. Article
  18. The ATM Kinase Restrains Joining of Both VDJ Signal and Coding Ends.Journal of immunology (Baltimore, Md. : 1950) · 2016
    Article
  19. Article
  20. Role of RAG1 autoubiquitination in V(D)J recombination.Proceedings of the National Academy of Sciences of the United States of America · 2015
    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

5 authors at 2 institutions in 2 countries.

Chao LuDepartment of Molecular Biology and Genetics and Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
Alyssa WardDepartment of Molecular Biology and Genetics and Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
John BettridgeDepartment of Molecular Biology and Genetics and Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Yun LiuDepartment of Molecular Biology and Genetics and Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Stephen DesiderioDepartment of Molecular Biology and Genetics and Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: sdesider@jhmi.edu.
Johns Hopkins Medicine · USJohns Hopkins University · US

Funding

BIOCHEMISTRY, CELLULAR AND MOLECULAR BIOLOGY PROGRAMT32GM007445 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI GREEN, RACHEL · 1985 to 2021
$24.1M
Temporal and Spatial Control of V(D)J RecombinationR01CA160256 · NCI · JOHNS HOPKINS UNIVERSITY · PI DESIDERIO, STEPHEN V · 2012 to 2016
$1.8M
NCI NIH HHS R01 CA160256NIGMS NIH HHS T32 GM007445
6 · The paper itself

Abstract

V(D)J recombination is initiated by a specialized transposase consisting of the subunits RAG-1 and RAG-2. The susceptibility of gene segments to DNA cleavage by the V(D)J recombinase is correlated with epigenetic modifications characteristic of active chromatin, including trimethylation of histone H3 on lysine 4 (H3K4me3). Engagement of H3K4me3 by a plant homeodomain (PHD) in RAG-2 promotes recombination in vivo and stimulates DNA cleavage by RAG in vitro. We now show that H3K4me3 acts allosterically at the PHD finger to relieve autoinhibition imposed by a separate domain within RAG-2. Disruption of this autoinhibitory domain was associated with constitutive increases in recombination frequency, DNA cleavage activity, substrate binding affinity, and catalytic rate, thus mimicking the stimulatory effects of H3K4me3. Our observations support a model in which allosteric control of RAG is enforced by an autoinhibitory domain whose action is relieved by engagement of active chromatin.

Indexed as

AnimalsBinding SitesChromatinDNA-Binding ProteinsHEK293 CellsHistone DemethylasesHistonesHomeodomain ProteinsHumansMethylationMiceNIH 3T3 CellsProtein BindingVDJ RecombinasesV(D)J RecombinationChromatinDNA-Binding ProteinsHistone DemethylasesHistonesHomeodomain ProteinsRAG-1 proteinVDJ RecombinasesV(D)J recombination activating protein 2

Identifiers

PMID25543141
PMCPMC4308961
OpenAlexW2091568014

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.