Evidence map›Paper›PMID 24987098›Full record

ArticleMolecular & cellular proteomics : MCP2014

Quantitative proteomic discovery of dynamic epigenome changes that control human cytomegalovirus (HCMV) infection.

Christine M O'Connor, Peter A DiMaggio, Thomas Shenk, Benjamin A Garcia

Open access · hybridAbstract read
In one paragraph

Article in Molecular & cellular proteomics : MCP, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

18 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. NADFrontiers in molecular biosciences · 2021
    Review
  6. Article
  7. Article
  8. Article
  9. Cellular responses to human cytomegalovirus infection: Induction of a mesenchymal-to-epithelial transition (MET) phenotype.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  10. The Promise of Proteomics in the Study of Oncogenic Viruses.Molecular & cellular proteomics : MCP · 2017
    Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. Article
  17. Article
  18. Review
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

4 authors at 4 institutions in 2 countries.

Christine M O'ConnorFrom the ‡Department of Molecular Genetics, Cleveland Clinic, Lerner Research Institute, Cleveland, Ohio 44195;
Peter A DiMaggio§Department of Chemical Engineering, Imperial College London, London, UK, SW7 2AZ;
Thomas Shenk¶Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544;
Benjamin A Garcia‖Epigenetics Program, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104 bgarci@mail.med.upenn.edu.
Cleveland Clinic Lerner College of Medicine · USImperial College London · GBPrinceton University · USUniversity of Pennsylvania · US

Funding

Novel Methodology for Quantitative High-throughput Cancer EpigeneticsDP2OD007447 · OD · UNIVERSITY OF PENNSYLVANIA · PI GARCIA, BENJAMIN A · 2010 to 2010
$2.4M
Human cytomegalovirus latency in cultured monocytesR01AI087672 · NIAID · PRINCETON UNIVERSITY · PI SHENK, THOMAS E · 2010 to 2014
$1.8M
A Proteomic Interrogation of the Histone Code during HCMV InfectionF32GM093490 · NIGMS · PRINCETON UNIVERSITY · PI DIMAGGIO, PETER A. · 2010 to 2011
$85k
NIAID NIH HHS AI87672NIAID NIH HHS R01 AI087672NIGMS NIH HHS F32 GM093490NIGMS NIH HHS F32GM093490NIH HHS DP2 OD007447
6 · The paper itself

Abstract

This work represents the first comprehensive quantitative analysis of global histone post-translational modifications (PTMs) from a virus infection, namely human cytomegalovirus (HCMV) infection. We used a nanoLC-MS/MS platform to identify and quantify the dynamic histone H3 and H4 PTMs expressed during HCMV replication in primary fibroblasts. Specifically, we examined the changes in histone PTMs over a 96 h time course to sample the immediate early (IE), early (E), and late (L) stages of viral infection. Several changes in histone H3 and H4 PTMs were observed, including a marked increase in H3K79me2 and H3K27me3K36me2, and a decrease in H4K16ac, highlighting likely epigenetic strategies of transcriptional activation and silencing during HCMV lytic infection. Heavy methyl-SILAC (hm-SILAC) was used to further confirm the histone methylation flux (especially for H3K79) during HCMV infection. We evaluated DOT1L (the H3K79 methyltransferase) mRNA levels in mock and HCMV-infected cells over a 96 h time course, and observed a significant increase in this methyltransferase as early as 24 hpi showing that viral infection up-regulates DOT1L expression, which drives H3K79me2. We then used shRNA to create a DOT1L knockdown cell population, and found that HCMV infection of the knockdown cells resulted in a 10-fold growth defect when compared with infected control cells not subjected to knockdown. This work documents multiple histone PTMs that occur in response to HCMV infection of fibroblasts, and provides a framework for evaluation of the role of epigenetic modifications in the virus-host interaction.

Indexed as

Protein Processing, Post-TranslationalCell LineChromatography, LiquidCytomegalovirusCytomegalovirus InfectionsDNA, ViralFibroblastsGene Knockdown TechniquesHistone-Lysine N-MethyltransferaseHistonesHumansMethyltransferasesProteomicsTandem Mass SpectrometryViral ProteinsVirus ReplicationDNA, ViralDOT1L protein, humanHistone-Lysine N-MethyltransferaseHistonesMethyltransferasesViral Proteins

Identifiers

PMID24987098
PMCPMC4159657
OpenAlexW2164537630

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.