Evidence map›Paper›PMID 22379087›Full record

ArticleJournal of virology2012

Genome-wide analysis of Epstein-Barr virus Rta DNA binding.

Andreas M F Heilmann, Michael A Calderwood, Daniel Portal, Yong Lu, Eric Johannsen

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.4field-weighted citation impact, top 10% 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

29 citing papers in PubMed, 41 citations in OpenAlex.

  1. Trial
  2. Review
  3. Multiple sclerosis and infection: history, EBV, and the search for mechanism.Microbiology and molecular biology reviews : MMBR · 2025
    Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Epstein-Barr virus-encoded microRNAs as regulators in host immune responses.International journal of biological sciences · 2018
    Review
  17. Article
  18. Article
  19. Review
  20. Article
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

5 authors at 2 institutions in 1 country.

Andreas M F HeilmannThe Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Michael A Calderwood
Daniel Portal
Yong Lu
Eric Johannsen
Brigham and Women's Hospital · USHarvard University · US

Funding

Genomic Analysis of Network Perturbations in Human DiseaseP50HG004233 · NHGRI · DANA-FARBER CANCER INST · PI VIDAL, MARC · 2007 to 2017
$31.6M
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
MOLECULAR BIOLOGY OF EPSTEIN-BARR VIRUS INFECTIONR35CA047006 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI KIEFF, ELLIOTT D · 1987 to 2000
$1.6M
Howard Hughes Medical InstituteNCI NIH HHS CA085180NCI NIH HHS CA47006NCI NIH HHS R01 CA047006NCI NIH HHS R01 CA085180NCI NIH HHS R35 CA047006NHGRI NIH HHS P50 HG004233NHGRI NIH HHS P50HG004233
6 · The paper itself

Abstract

The Epstein-Barr virus (EBV) lytic transactivator Rta activates promoters through direct binding to cognate DNA sites termed Rta response elements (RREs). Rta also activates promoters that apparently lack Rta binding sites, notably Zp and Rp. Chromatin immunoprecipitation (ChIP) of endogenous Rta expressed during early replication in B95-8 cells was performed to identify Rta binding sites in the EBV genome. Quantitative PCR (qPCR) analysis showed strong enrichment for known RREs but little or no enrichment for Rp or Zp, suggesting that the Rta ChIP approach enriches for direct Rta binding sites. Rta ChIP combined with deep sequencing (ChIP-seq) identified most known RREs and several novel Rta binding sites. Rta ChIP-seq peaks were frequently upstream of Rta-responsive genes, indicating that these Rta binding sites are likely functioning as RREs. Unexpectedly, the BALF5 promoter contained an Rta binding peak. To assess whether BALF5 might be activated by an RRE-dependent mechanism, an Rta mutant (Rta K156A), deficient for DNA binding and RRE activation but competent for Zp/Rp activation, was used. Rta K156A failed to activate BALF5p, suggesting this promoter can be activated by an RRE-dependent mechanism. Rta binding to late gene promoters was not seen at early time points but was specifically detected at later times within the Rta-responsive BLRF2 and BFRF3 promoters, even when DNA replication was inhibited. Our results represent the first characterization of Rta binding to the EBV genome during replication, identify previously unknown RREs, such as one in BALF5p, and highlight the complexity of EBV late gene promoter activation by Rta.

Indexed as

Binding SitesCell LineDNA-Binding ProteinsDNA-Directed DNA PolymeraseDNA ReplicationDNA, ViralGenome, ViralHerpesvirus 4, HumanHumansImmediate-Early ProteinsMutationPromoter Regions, GeneticProtein Interaction Domains and MotifsResponse ElementsTrans-ActivatorsViral ProteinsBALF5 protein, Epstein-barr virusBRLF1 protein, Human herpesvirus 4DNA-Binding ProteinsDNA-Directed DNA PolymeraseDNA, ViralImmediate-Early ProteinsTrans-ActivatorsViral Proteins

Identifiers

PMID22379087
PMCPMC3347379
OpenAlexW2166647725

What OpenQuestion 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 OpenQuestion graph.