Evidence map›Paper›PMID 21737748›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2011

Genome-wide analysis reveals conserved and divergent features of Notch1/RBPJ binding in human and murine T-lymphoblastic leukemia cells.

Hongfang Wang, James Zou, Bo Zhao, Eric Johannsen, Todd Ashworth, Hoifung Wong, Warren S Pear, Jonathan Schug, Stephen C Blacklow, Kelly L Arnett and 3 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 166 papers.

0numbers the graph read from it
0cells of the map it votes in
166citing papers in PubMed
10.0field-weighted citation impact, top 1% 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

166 citing papers in PubMed, 239 citations in OpenAlex.

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  10. Reciprocal suppression between TGFβ signaling and TNF stimulation finetunes the macrophage inflammatory response.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Article
  11. Article
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  15. Article
  16. Review
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  18. Notch Partners in the Long Journey of T-ALL Pathogenesis.International journal of molecular sciences · 2023
    Review
  19. Article
  20. Article

106 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 5 institutions in 1 country.

Hongfang WangDepartment of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
James Zou
Bo Zhao
Eric Johannsen
Todd Ashworth
Hoifung Wong
Warren S Pear
Jonathan Schug
Stephen C Blacklow
Kelly L Arnett
Bradley E Bernstein
Elliott Kieff
Jon C Aster
Brigham and Women's Hospital · USDana-Farber Cancer Institute · USUniversity of Pennsylvania · USHarvard University · USHoward Hughes Medical Institute · US

Funding

VIRAL VECTOR COREP30DK019525 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI Patrick Seale · 1986 to 2026
$48.3M
Production sequencing of reference human epigenomesU01ES017155 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BERNSTEIN, BRADLEY EVAN, MEISSNER, ALEXANDER · 2008 to 2012
$15.4M
Epstein-Barr Virus Nuclear Proteins in B Cell Growth TransformationR01CA047006 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ZHAO, BO · 2002 to 2021
$12.1M
Epstein-Barr Virus LMP-1 Mediated OncongenicityR01CA085180 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI KIEFF, ELLIOTT D · 2000 to 2016
$10.6M
Protein CoreP01CA119070 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ASTER, JON C. · 2006 to 2016
$10.3M
High-throughput sequencing of chromatin regulatory elementsU54HG004570 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BERNSTEIN, BRADLEY EVAN · 2007 to 2011
$8.1M
Inhibitors of Epstein-Barr Virus Nuclear Protein 1 Mediated Latent InfectionR01CA131354 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI KIEFF, ELLIOTT D · 2009 to 2013
$1.8M
Howard Hughes Medical InstituteNCI NIH HHS P01 CA119070NCI NIH HHS P01CA119070NCI NIH HHS R01 CA047006NCI NIH HHS R01CA047006NCI NIH HHS R01 CA085180NCI NIH HHS R01 CA131354NCI NIH HHS R01CA131354NHGRI NIH HHS U54 HG004570NIDDK NIH HHS P30 DK019525NIDDK NIH HHS P30-DK19525NIEHS NIH HHS U01 ES017155
6 · The paper itself

Abstract

Notch1 regulates gene expression by associating with the DNA-binding factor RBPJ and is oncogenic in murine and human T-cell progenitors. Using ChIP-Seq, we find that in human and murine T-lymphoblastic leukemia (TLL) genomes Notch1 binds preferentially to promoters, to RBPJ binding sites, and near imputed ZNF143, ETS, and RUNX sites. ChIP-Seq confirmed that ZNF143 binds to ∼40% of Notch1 sites. Notch1/ZNF143 sites are characterized by high Notch1 and ZNF143 signals, frequent cobinding of RBPJ (generally through sites embedded within ZNF143 motifs), strong promoter bias, and relatively low mean levels of activating chromatin marks. RBPJ and ZNF143 binding to DNA is mutually exclusive in vitro, suggesting RBPJ/Notch1 and ZNF143 complexes exchange on these sites in cells. K-means clustering of Notch1 binding sites and associated motifs identified conserved Notch1-RUNX, Notch1-ETS, Notch1-RBPJ, Notch1-ZNF143, and Notch1-ZNF143-ETS clusters with different genomic distributions and levels of chromatin marks. Although Notch1 binds mainly to gene promoters, ∼75% of direct target genes lack promoter binding and are presumably regulated by enhancers, which were identified near MYC, DTX1, IGF1R, IL7R, and the GIMAP cluster. Human and murine TLL genomes also have many sites that bind only RBPJ. Murine RBPJ-only sites are highly enriched for imputed REST (a DNA-binding transcriptional repressor) sites, whereas human RPBJ-only sites lack REST motifs and are more highly enriched for imputed CREB sites. Thus, there is a conserved network of cis-regulatory factors that interacts with Notch1 to regulate gene expression in TLL cells, as well as unique classes of divergent RBPJ-only sites that also likely regulate transcription.

Indexed as

Gene Expression Regulation, LeukemicGenome, HumanResponse ElementsAnimalsCell Line, TumorChromatinGenome-Wide Association StudyHumansImmunoglobulin J Recombination Signal Sequence-Binding ProteinLeukemia, T-CellMiceNeoplasm ProteinsReceptor, Notch1Transcription, GeneticChromatinImmunoglobulin J Recombination Signal Sequence-Binding ProteinNeoplasm ProteinsNOTCH1 protein, humanNotch1 protein, mouseRBPJ protein, humanRbpj protein, mouseReceptor, Notch1

Identifiers

PMID21737748
PMCPMC3169118
OpenAlexW1977582022

What Socratic 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 Socratic graph.