Evidence map›Paper›PMID 27889452›Full record

ArticleMolecular cell2016

An RB-EZH2 Complex Mediates Silencing of Repetitive DNA Sequences.

Charles A Ishak, Aren E Marshall, Daniel T Passos, Carlee R White, Seung J Kim, Matthew J Cecchini, Sara Ferwati, William A MacDonald, Christopher J Howlett, Ian D Welch and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.

0numbers the graph read from it
0cells of the map it votes in
112citing papers in PubMed
8.2field-weighted citation impact, top 2% 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

112 citing papers in PubMed, 166 citations in OpenAlex.

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  16. LINE-1 retrotransposon activation drives age-associated inflammationContemporary oncology (Poznan, Poland) · 2025
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52 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 4 institutions in 2 countries.

Charles A IshakLondon Regional Cancer Program, London, ON N6A 4L6, Canada; Department of Biochemistry, Western University, London, ON N6A 3K7, Canada.
Aren E MarshallLondon Regional Cancer Program, London, ON N6A 4L6, Canada; Department of Biochemistry, Western University, London, ON N6A 3K7, Canada.
Daniel T PassosLondon Regional Cancer Program, London, ON N6A 4L6, Canada; Department of Biochemistry, Western University, London, ON N6A 3K7, Canada.
Carlee R WhiteChildren's Health Research Institute, London, ON N6A 4L6, Canada; Department of Biochemistry, Western University, London, ON N6A 3K7, Canada.
Seung J KimLondon Regional Cancer Program, London, ON N6A 4L6, Canada; Department of Biochemistry, Western University, London, ON N6A 3K7, Canada.
Matthew J CecchiniLondon Regional Cancer Program, London, ON N6A 4L6, Canada; Department of Pathology and Laboratory Medicine, Western University, London, ON N6A 3K7, Canada.
Sara FerwatiLondon Regional Cancer Program, London, ON N6A 4L6, Canada; Department of Biochemistry, Western University, London, ON N6A 3K7, Canada.
William A MacDonaldMagee-Womens Research Institute, Pittsburgh, PA 15213, USA; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Christopher J HowlettDepartment of Pathology and Laboratory Medicine, Western University, London, ON N6A 3K7, Canada.
Ian D WelchAnimal Care Services, University of British Columbia, Vancouver, BC V6T1Z4, Canada.
Seth M RubinDepartment of Chemistry and Biochemistry, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
Mellissa R W MannMagee-Womens Research Institute, Pittsburgh, PA 15213, USA; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Frederick A DickLondon Regional Cancer Program, London, ON N6A 4L6, Canada; Children's Health Research Institute, London, ON N6A 4L6, Canada; Department of Biochemistry, Western University, London, ON N6A 3K7, Canada. Electronic address: fdick@uwo.ca.
Western University · CAUniversity of Pittsburgh · USUniversity of British Columbia · CAUniversity of California, Santa Cruz · US

Funding

Molecular Mechanisms Regulating the Retinoblastoma Protein FamilyR01CA132685 · NCI · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI RUBIN, SETH MICHAEL · 2008 to 2017
$3.0M
CIHR MOP-64253CIHR MOP-89765NCI NIH HHS R01 CA132685
6 · The paper itself

Abstract

Repetitive genomic regions include tandem sequence repeats and interspersed repeats, such as endogenous retroviruses and LINE-1 elements. Repressive heterochromatin domains silence expression of these sequences through mechanisms that remain poorly understood. Here, we present evidence that the retinoblastoma protein (pRB) utilizes a cell-cycle-independent interaction with E2F1 to recruit enhancer of zeste homolog 2 (EZH2) to diverse repeat sequences. These include simple repeats, satellites, LINEs, and endogenous retroviruses as well as transposon fragments. We generated a mutant mouse strain carrying an F832A mutation in Rb1 that is defective for recruitment to repetitive sequences. Loss of pRB-EZH2 complexes from repeats disperses H3K27me3 from these genomic locations and permits repeat expression. Consistent with maintenance of H3K27me3 at the Hox clusters, these mice are developmentally normal. However, susceptibility to lymphoma suggests that pRB-EZH2 recruitment to repetitive elements may be cancer relevant.

Indexed as

Gene SilencingRepetitive Sequences, Nucleic AcidAnimalsCarcinoma, HepatocellularE2F1 Transcription FactorEnhancer of Zeste Homolog 2 ProteinFibroblastsGenetic Predisposition to DiseaseHistonesLiver NeoplasmsLymphomaMesenteryMiceMutationPrimary Cell CultureProtein BindingE2f1 protein, mouseE2F1 Transcription FactorEnhancer of Zeste Homolog 2 ProteinEzh2 protein, mouseHistonesRetinoblastoma ProteincancerepigeneticsH3K27me3heterochromatinPolycombrepetitive DNAretinoblastoma protein

Identifiers

PMID27889452
PMCPMC5340194
OpenAlexW2552764510

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.