Evidence map›Paper›PMID 18094192›Full record

ArticleJournal of virology2008

Identification of cellular proteins that maintain retroviral epigenetic silencing: evidence for an antiviral response.

Andrey Poleshko, Ivan Palagin, Rugang Zhang, Pamela Boimel, Carolyn Castagna, Peter D Adams, Anna Marie Skalka, Richard A Katz

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
1.2field-weighted citation impact, top 27% 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

27 citing papers in PubMed, 44 citations in OpenAlex.

  1. Trial
  2. Review
  3. Review
  4. Article
  5. Article
  6. Roles of the CSE1L-mediated nuclear import pathway in epigenetic silencing.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. Evaluating risks of insertional mutagenesis by DNA transposons in gene therapy.Translational research : the journal of laboratory and clinical medicine · 2013
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  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

8 authors at 1 institution in 1 country.

Andrey PoleshkoFox Chase Cancer Center, Institute for Cancer Research, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
Ivan Palagin
Rugang Zhang
Pamela Boimel
Carolyn Castagna
Peter D Adams
Anna Marie Skalka
Richard A Katz
Fox Chase Cancer Center · US

Funding

WORD PROCESSING CENTER--COREP30CA006927 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI Eric Andrew Ross · 1985 to 2026
$138.8M
INTEGRATION OF RETROVIRAL DNA--ACCESSING HOST TARGET DNAR01CA071515 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI KATZ, RICHARD ALAN · 1996 to 2016
$7.6M
GFP-Based Assays to Probe Transcriptional Controls(RMI)R21NS053666 · NINDS · INSTITUTE FOR CANCER RESEARCH · PI KATZ, RICHARD ALAN · 2005 to 2005
$211k
NCI NIH HHS CA06927NCI NIH HHS CA71515NCI NIH HHS P30 CA006927NCI NIH HHS R01 CA071515NINDS NIH HHS NS053666NINDS NIH HHS R21 NS053666
6 · The paper itself

Abstract

Integrated retroviral DNA is subject to epigenetic gene silencing, resulting in loss of expression of viral genes as well as reporter or therapeutic genes transduced by retroviral vectors. Possible mediators of such silencing include the histone deacetylase (HDAC) family of cellular proteins. We previously isolated HeLa cell populations that harbored silent avian sarcoma virus-based green fluorescent protein (GFP) vectors that could be reactivated by treatment with HDAC inhibitors. Here, we developed a small interfering RNA (siRNA)-based approach to identify specific host factors that participate in the maintenance of silencing. Knockdown of HDAC1, the transcriptional repressor Daxx (a binding partner of HDAC1), or heterochromatin protein 1 gamma resulted in robust and specific GFP reporter gene reactivation. Analyses of cell clones and diverse GFP vector constructs revealed that the roles of HDAC1 and Daxx in retroviral silencing are largely independent of the integration site or the promoter controlling the silent GFP reporter gene. Previous findings from our laboratory and those of others have suggested that Daxx and HDAC proteins may act broadly as part of an antiviral response to repress viral gene transcription. Expression of presumptive viral "countermeasure" proteins that are known to inhibit Daxx or HDACs (pp71, IE2, and Gam1) resulted in the reactivation of GFP reporter gene expression. This study has identified individual host factors that maintain retroviral silencing and supports the proposal that these factors participate in an antiviral response. Furthermore, our results indicate that siRNAs can be used as specific reagents to interrupt the maintenance of epigenetic silencing.

Indexed as

Adaptor Proteins, Signal TransducingBase SequenceChromobox Protein Homolog 5Chromosomal Proteins, Non-HistoneCo-Repressor ProteinsDNA PrimersEpigenesis, GeneticGene SilencingHeLa CellsHistone Deacetylase InhibitorsHistone DeacetylasesHumansMolecular ChaperonesNuclear ProteinsPromoter Regions, GeneticProteinsAdaptor Proteins, Signal TransducingChromobox Protein Homolog 5Chromosomal Proteins, Non-HistoneCo-Repressor ProteinsDAXX protein, humanDNA PrimersHistone Deacetylase InhibitorsHistone DeacetylasesMolecular ChaperonesNuclear ProteinsProteinsRNA, Small Interfering

Identifiers

PMID18094192
PMCPMC2258957
OpenAlexW2015676288

What Socratic 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 Socratic graph.