Evidence map›Paper›PMID 27698124›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Regulated large-scale nucleosome density patterns and precise nucleosome positioning correlate with V(D)J recombination.

Sandhya R Pulivarthy, Mattia Lion, Guray Kuzu, Adam G W Matthews, Mark L Borowsky, John Morris, Robert E Kingston, Jonathan H Dennis, Michael Y Tolstorukov, Marjorie A Oettinger

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing 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

21 citing papers in PubMed, 45 citations in OpenAlex.

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  15. Alterations in chromatin at antigen receptor loci define lineage progression during B lymphopoiesis.Proceedings of the National Academy of Sciences of the United States of America · 2020
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  18. A new twist on V(D)J recombination.Nature structural & molecular biology · 2018
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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

10 authors at 2 institutions in 1 country.

Sandhya R PulivarthyDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114; Department of Genetics, Harvard Medical School, Boston, MA 02115.
Mattia LionDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114; Department of Genetics, Harvard Medical School, Boston, MA 02115.
Guray KuzuDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114.
Adam G W MatthewsDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114; Department of Genetics, Harvard Medical School, Boston, MA 02115; Department of Biological Sciences, Wellesley College, Wellesley, MA 02481; Program in Biochemistry, Wellesley College, Wellesley, MA 02481.
Mark L BorowskyDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114; Department of Genetics, Harvard Medical School, Boston, MA 02115.
John MorrisDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114; Department of Genetics, Harvard Medical School, Boston, MA 02115.
Robert E KingstonDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114; Department of Genetics, Harvard Medical School, Boston, MA 02115.
Jonathan H DennisDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114; Department of Genetics, Harvard Medical School, Boston, MA 02115; Department of Biological Science, Florida State University, Tallahassee, FL 32306.
Michael Y TolstorukovDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114; tolstorukov@molbio.mgh.harvard.edu oettinger@molbio.mgh.harvard.edu.
Marjorie A OettingerDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114; Department of Genetics, Harvard Medical School, Boston, MA 02115; tolstorukov@molbio.mgh.harvard.edu oettinger@molbio.mgh.harvard.edu.
Harvard University · USMassachusetts General Hospital · US

Funding

A Systems-level Approach to Studying HIV/AIDS Susceptibility and Substance AbuseR01DA033773 · NIDA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI WOLINSKY, STEVEN M · 2012 to 2016
$4.6M
Transcription Factor Interactions with NucleosomesR37GM048405 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI KINGSTON, ROBERT · 2009 to 2018
$3.9M
VDJ RECOMBINATION ACTIVATING GENES--FUNCTIONAL ANALYSISR01GM048026 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI OETTINGER, MARJORIE A · 1992 to 2009
$3.5M
TRANSCRIPTION FACTOR INTERACTIONS WITH NUCLEOSOMESR01GM048405 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI KINGSTON, ROBERT · 1993 to 2008
$3.1M
Functional role of RAG2 H3K4me3 interaction in V(D)J recombinationR01AI083510 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI OETTINGER, MARJORIE A · 2010 to 2014
$2.2M
Functional role of RAG2 H3K4me3 interaction in V(D)J recombinationR56AI083510 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI OETTINGER, MARJORIE A · 2009 to 2009
$211k
NIAID NIH HHS R01 AI083510NIAID NIH HHS R56 AI083510NIDA NIH HHS R01 DA033773NIGMS NIH HHS R01 GM048026NIGMS NIH HHS R01 GM048405NIGMS NIH HHS R37 GM048405
6 · The paper itself

Abstract

We show that the physical distribution of nucleosomes at antigen receptor loci is subject to regulated cell type-specific and lineage-specific positioning and correlates with the accessibility of these gene segments to recombination. At the Ig heavy chain locus (IgH), a nucleosome in pro-B cells is generally positioned over each IgH variable (VH) coding segment, directly adjacent to the recombination signal sequence (RSS), placing the RSS in a position accessible to the recombination activating gene (RAG) recombinase. These changes result in establishment of a specific chromatin organization at the RSS that facilitates accessibility of the genomic DNA for the RAG recombinase. In contrast, in mouse embryonic fibroblasts the coding segment is depleted of nucleosomes, which instead cover the RSS, thereby rendering it inaccessible. Pro-T cells exhibit a pattern intermediate between pro-B cells and mouse embryonic fibroblasts. We also find large-scale variations of nucleosome density over hundreds of kilobases, delineating chromosomal domains within IgH, in a cell type-dependent manner. These findings suggest that developmentally regulated changes in nucleosome location and occupancy, in addition to the known chromatin modifications, play a fundamental role in regulating V(D)J recombination. Nucleosome positioning-which has previously been observed to vary locally at individual enhancers and promoters-may be a more general mechanism by which cells can regulate the accessibility of the genome during development, at scales ranging from several hundred base pairs to many kilobases.

Indexed as

V(D)J RecombinationAnimalsCell LineChromatinChromatin Assembly and DisassemblyChromatin ImmunoprecipitationChromosome MappingDNA-Binding ProteinsEpigenomicsGene Knockout TechniquesGenetic LociHigh-Throughput Nucleotide SequencingImmunoglobulin Heavy ChainsImmunoglobulin Variable RegionLymphocytesMiceChromatinDNA-Binding ProteinsImmunoglobulin Heavy ChainsImmunoglobulin Variable RegionNucleosomesRag2 protein, mouseReceptors, Antigen, T-Cell, alpha-betachromatinepigeneticslymphocytesnucleosome positioningV(D)J recombination

Identifiers

PMID27698124
PMCPMC5081657
OpenAlexW2528563747

What OpenQuestion holds

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Registered trials

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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.