Evidence map›Paper›PMID 23320978›Full record

ArticleGenome biology2013

The B cell transcription program mediates hypomethylation and overexpression of key genes in Epstein-Barr virus-associated proliferative conversion.

Henar Hernando, Claire Shannon-Lowe, Abul B Islam, Fatima Al-Shahrour, Javier Rodríguez-Ubreva, Virginia C Rodríguez-Cortez, Biola M Javierre, Cristina Mangas, Agustín F Fernández, Maribel Parra and 6 more

Open access · goldAbstract read
In one paragraph

Article in Genome biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 1 pooled it
2.8field-weighted citation impact, top 9% 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

33 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.

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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

16 authors at 8 institutions in 4 countries.

Henar Hernando
Claire Shannon-Lowe
Abul B Islam
Fatima Al-Shahrour
Javier Rodríguez-Ubreva
Virginia C Rodríguez-Cortez
Biola M Javierre
Cristina Mangas
Agustín F Fernández
Maribel Parra
Henri-Jacques Delecluse
Manel Esteller
Eduardo López-Granados
Mario F Fraga
Nuria López-Bigas
Esteban Ballestar
Institut d'Investigació Biomédica de Bellvitge · ESUniversidad de Oviedo · ESBarcelona Biomedical Research Park · ESBroad Institute · USHeidelberg University · DEHospital Universitario La Paz · ESPompeu Fabra University · ESUniversity of Birmingham · GB

Funding

Medical Research Council MR/J002046/1
6 · The paper itself

Abstract

backgroundEpstein-Barr virus (EBV) infection is a well characterized etiopathogenic factor for a variety of immune-related conditions, including lymphomas, lymphoproliferative disorders and autoimmune diseases. EBV-mediated transformation of resting B cells to proliferating lymphoblastoid cells occurs in early stages of infection and is an excellent model for investigating the mechanisms associated with acquisition of unlimited growth.

resultsWe investigated the effects of experimental EBV infection of B cells on DNA methylation profiles by using high-throughput analysis. Remarkably, we observed hypomethylation of around 250 genes, but no hypermethylation. Hypomethylation did not occur at repetitive sequences, consistent with the absence of genomic instability in lymphoproliferative cells. Changes in methylation only occurred after cell divisions started, without the participation of the active demethylation machinery, and were concomitant with acquisition by B cells of the ability to proliferate. Gene Ontology analysis, expression profiling, and high-throughput analysis of the presence of transcription factor binding motifs and occupancy revealed that most genes undergoing hypomethylation are active and display the presence of NF-κB p65 and other B cell-specific transcription factors. Promoter hypomethylation was associated with upregulation of genes relevant for the phenotype of proliferating lymphoblasts. Interestingly, pharmacologically induced demethylation increased the efficiency of transformation of resting B cells to lymphoblastoid cells, consistent with productive cooperation between hypomethylation and lymphocyte proliferation.

conclusionsOur data provide novel clues on the role of the B cell transcription program leading to DNA methylation changes, which we find to be key to the EBV-associated conversion of resting B cells to proliferating lymphoblasts.

Indexed as

DNA MethylationLymphocyte ActivationTranscription, GeneticB-LymphocytesCell ProliferationEpstein-Barr Virus InfectionsGene Expression ProfilingHumansUp-Regulation

Identifiers

PMID23320978
PMCPMC3663113
OpenAlexW2141125218

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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.