ArticleMolecular and cellular biology2006
Role for centromeric heterochromatin and PML nuclear bodies in the cellular response to foreign DNA.
Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers.
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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.
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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.
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Who cites it
14 citing papers in PubMed, 36 citations in OpenAlex.
- PML-NB-dependent type I interferon memory results in a restricted form of HSV latency.EMBO reports · 2021Article
- PML nuclear bodies and chromatin dynamics: catch me if you can!Nucleic acids research · 2020Review
- The histone deacetylase inhibitor Entinostat enhances polymer-mediated transgene expression in cancer cell lines.Biotechnology and bioengineering · 2016Article
- An Adenovirus DNA Replication Factor, but Not Incoming Genome Complexes, Targets PML Nuclear Bodies.Journal of virology · 2016Article
- Alterations of Nuclear Architecture and Epigenetic Signatures during African Swine Fever Virus Infection.Viruses · 2015Article
- Article
- Differential type I interferon-dependent transgene silencing of helper-dependent adenoviral vs. adeno-associated viral vectors in vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2013Article
- Histone deacetylase inhibition activates transgene expression from integration-defective lentiviral vectors in dividing and non-dividing cells.Human gene therapy · 2013Article
- HSV-1 genome subnuclear positioning and associations with host-cell PML-NBs and centromeres regulate LAT locus transcription during latency in neurons.PLoS pathogens · 2012Article
- Recognition and suppression of transfected plasmids by protein ZNF511-PRAP1, a potential molecular barrier to transgene expression.Molecular therapy : the journal of the American Society of Gene Therapy · 2011Article
- Functional nuclear topography of transcriptionally inducible extra-chromosomal transgene clusters.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2010Article
- PML has a predictive role in tumor cell permissiveness to interferon-sensitive oncolytic viruses.Gene therapy · 2009Article
- Quantitation of human seroresponsiveness to Merkel cell polyomavirus.PLoS pathogens · 2009Article
- Imaging single virus particles on the surface of cell membranes by high-resolution scanning surface confocal microscopy.Biophysical journal · 2008Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nuclear spatial positioning plays an important role in the epigenetic regulation of eukaryotic gene expression. Here we show a role for nuclear spatial positioning in regulating episomal transgenes that are delivered by virus-like particles (VLPs). VLPs mediate the delivery of plasmid DNA (pDNA) to cell nuclei but lack viral factors involved in initiating and regulating transcription. By tracking single fluorescently labeled VLPs, coupled with luciferase reporter gene assays, we found that VLPs transported pDNA to cell nuclei efficiently but transgenes were immediately silenced by the cell. An investigation of the nuclear location of fluorescent VLPs revealed that the pDNAs were positioned next to centromeric heterochromatin. The activation of transcription by providing viral factors or inhibiting histone deacetylase activity resulted in the localization to euchromatin regions. Further, the activation of transcription induced the recruitment of PML nuclear bodies (PML-NBs) to the VLPs. This association did not play a role in regulating transgene expression, but PML protein was necessary for the inhibition of transgene expression with alpha interferon (IFN-alpha). These results support a model whereby cells can prevent foreign gene expression at two levels: by positioning transgenes next to centromeric heterochromatin or, if that is overcome, via the type I IFN response facilitated by PML-NB recruitment.
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Registered trials
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.