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

Overview of attention for article published in Genome Biology, January 2013
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Title
The B cell transcription program mediates hypomethylation and overexpression of key genes in Epstein-Barr virus-associated proliferative conversion
Published in
Genome Biology, January 2013
DOI 10.1186/gb-2013-14-1-r3
Pubmed ID
Authors

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

Abstract

BACKGROUND: Epstein-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. RESULTS: We 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. CONCLUSIONS: Our 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.

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X Demographics

The data shown below were collected from the profiles of 9 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 63 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 2 3%
Spain 1 2%
Luxembourg 1 2%
Unknown 59 94%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 17 27%
Researcher 8 13%
Student > Doctoral Student 7 11%
Student > Bachelor 5 8%
Student > Master 5 8%
Other 11 17%
Unknown 10 16%
Readers by discipline Count As %
Agricultural and Biological Sciences 26 41%
Biochemistry, Genetics and Molecular Biology 12 19%
Medicine and Dentistry 5 8%
Immunology and Microbiology 3 5%
Mathematics 1 2%
Other 4 6%
Unknown 12 19%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 6. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 April 2015.
All research outputs
#6,571,272
of 25,373,627 outputs
Outputs from Genome Biology
#3,131
of 4,467 outputs
Outputs of similar age
#68,388
of 307,792 outputs
Outputs of similar age from Genome Biology
#33
of 50 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. This one has received more attention than most of these and is in the 74th percentile.
So far Altmetric has tracked 4,467 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 27.6. This one is in the 29th percentile – i.e., 29% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 307,792 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 77% of its contemporaries.
We're also able to compare this research output to 50 others from the same source and published within six weeks on either side of this one. This one is in the 34th percentile – i.e., 34% of its contemporaries scored the same or lower than it.