Evidence map›Paper›PMID 9420232›Full record

ArticleJournal of virology1998

Host cis-mediated extinction of a retrovirus permissive for expression in embryonal stem cells during differentiation.

C Laker, J Meyer, A Schopen, J Friel, C Heberlein, W Ostertag, C Stocking

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
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

49 citing papers in PubMed, 105 citations in OpenAlex.

  1. Article
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  3. Alopecia in Harlequin mutant mice is associated with reduced AIF protein levels and expression of retroviral elements.Mammalian genome : official journal of the International Mammalian Genome Society · 2021
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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

7 authors at 2 institutions in 1 country.

C LakerAbteilung für Zell- und Virusgenetik, Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie an der Universität Hamburg, Germany.
J Meyer
A Schopen
J Friel
C Heberlein
W Ostertag
C Stocking
Universität Hamburg · DELeibniz Institute of Virology (LIV) · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The use of retroviral vectors for gene transfer into animals has been severely hampered by the lack of provirus transcription in the early embryo and embryonic stem (ES) cells. This primary block in provirus expression is maintained in differentiated cells by a cis-acting mechanism that is not well characterized. Retroviral vectors based on the murine embryonal stem cell virus (MESV), which overcome the transcriptional block in ES cells, were constructed to investigate this secondary mechanism. These vectors transferred G418 resistance to ES cells with the same efficiency as to fibroblasts, but overall transcript levels were greatly reduced. A mosaic but stable expression pattern was observed when single cells from G418-resistant clones were replated in G418 or assayed for expression of LacZ or interleukin-3. The expression levels in independent clones were variable and correlated inversely with methylation. However, a second, more pronounced, block to transcription was found upon differentiation induction. Differentiation of the infected ES cells to cells permissive for retroviral expression resulted in repression and complete extinction of provirus expression. Extinction was not accompanied by increased levels of methylation. Provirus expression is thus regulated by two independent cis-acting mechanisms: (i) partial repression in the undifferentiated state, accompanied by increased methylation but compatible with long-term, low expression of retroviral genes, and (ii) total repression and extinction during early stages of differentiation, apparently independent of changes in methylation. These results indicate a time window early during the transition from an undifferentiated to a differentiated stage in which provirus expression is silenced. The mechanisms are presently unknown, but elucidation of these events will have an important impact on vector development for targeting stem cells and for gene therapy.

Indexed as

Genetic VectorsAnimalsBase SequenceCell DifferentiationCells, CulturedDNA MethylationDNA, ViralEnhancer Elements, GeneticGene Expression Regulation, DevelopmentalGenes, ViralGene Transfer TechniquesMiceMosaicismMutationPromoter Regions, GeneticProvirusesDNA, Viral

Identifiers

PMID9420232
PMCPMC109381
OpenAlexW2111055181

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.