Evidence map›Paper›PMID 24830456›Full record

ArticlePLoS pathogens2014

RETRACTED: The downregulation of GFI1 by the EZH2-NDY1/KDM2B-JARID2 axis and by human cytomegalovirus (HCMV) associated factors allows the activation of the HCMV major IE promoter and the transition to productive infection.

George Sourvinos, Antigoni Morou, Ioannis Sanidas, Ignea Codruta, Scott A Ezell, Christina Doxaki, Sotirios C Kampranis, Filippos Kottakis, Philip N Tsichlis

RetractedOpen access · goldAbstract readRetracted Publication
In one paragraph

Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

15 citing papers in PubMed, 21 citations in OpenAlex.

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  11. Expanding the Known Functional Repertoire of the Human Cytomegalovirus pp71 Protein.Frontiers in cellular and infection microbiology · 2020
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 2 countries.

George SourvinosMolecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts, United States of America; Laboratory of Virology, Medical School, University of Crete, Heraklion, Crete, Greece.
Antigoni MorouLaboratory of Virology, Medical School, University of Crete, Heraklion, Crete, Greece.
Ioannis SanidasMolecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts, United States of America.
Ignea CodrutaLaboratory of Biochemistry, Medical School, University of Crete, Heraklion, Crete, Greece.
Scott A EzellMolecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts, United States of America.
Christina DoxakiLaboratory of Biochemistry, Medical School, University of Crete, Heraklion, Crete, Greece.
Sotirios C KampranisMolecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts, United States of America; Laboratory of Biochemistry, Medical School, University of Crete, Heraklion, Crete, Greece.
Filippos KottakisMolecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts, United States of America.
Philip N TsichlisMolecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts, United States of America.
Tufts Medical Center · USUniversity of Crete · GR

Funding

The role of Ndy1 in epigenetic gene silencing and stem cell biologyR01CA109747 · NCI · TUFTS MEDICAL CENTER · PI TSICHLIS, PHILIP N. · 2004 to 2010
$2.0M
NCI NIH HHS R01 CA109747
6 · The paper itself

Abstract

Earlier studies had suggested that epigenetic mechanisms play an important role in the control of human cytomegalovirus (HCMV) infection. Here we show that productive HCMV infection is indeed under the control of histone H3K27 trimethylation. The histone H3K27 methyltransferase EZH2, and its regulators JARID2 and NDY1/KDM2B repress GFI1, a transcriptional repressor of the major immediate-early promoter (MIEP) of HCMV. Knocking down EZH2, NDY1/KDM2B or JARID2 relieves the repression and results in the upregulation of GFI1. During infection, the incoming HCMV rapidly downregulates the GFI1 mRNA and protein in both wild-type cells and in cells in which EZH2, NDY1/KDM2B or JARID2 were knocked down. However, since the pre-infection levels of GFI1 in the latter cells are significantly higher, the virus fails to downregulate it to levels permissive for MIEP activation and viral infection. Following the EZH2-NDY1/KDM2B-JARID2-independent downregulation of GFI1 in the early stages of infection, the virus also initiates an EZH2-NDY1/ΚDM2Β-JARID2-dependent program that represses GFI1 throughout the infection cycle. The EZH2 knockdown also delays histone H3K27 trimethylation in the immediate early region of HCMV, which is accompanied by a drop in H3K4 trimethylation that may contribute to the shEZH2-mediated repression of the major immediate early HCMV promoter. These data show that HCMV uses multiple mechanisms to allow the activation of the HCMV MIEP and to prevent cellular mechanisms from blocking the HCMV replication program.

Indexed as

Cytomegalovirus InfectionsPromoter Regions, GeneticAntigens, ViralCells, CulturedCytomegalovirusDNA-Binding ProteinsDown-RegulationEnhancer of Zeste Homolog 2 ProteinF-Box ProteinsHEK293 CellsHeLa CellsHumansImmediate-Early ProteinsJumonji Domain-Containing Histone DemethylasesPolycomb Repressive Complex 2Signal TransductionAntigens, ViralDNA-Binding ProteinsEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanF-Box ProteinsGFI1 protein, humanImmediate-Early Proteinsimmediate-early proteins, cytomegalovirusJARID2 protein, humanJumonji Domain-Containing Histone DemethylasesKdm2b protein, mousePolycomb Repressive Complex 2Transcription FactorsViral Proteins

Identifiers

PMID24830456
PMCPMC4022736
OpenAlexW2009590608

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.