ArticleJournal of virology2005
Dynamic DNA methylation and histone modifications contribute to lentiviral transgene silencing in murine embryonic carcinoma cells.
Article in Journal of virology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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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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Who cites it
37 citing papers in PubMed, 70 citations in OpenAlex.
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- A synthetic circuit for buffering gene dosage variation between individual mammalian cells.Nature communications · 2021Article
- Searching for Promoters to Drive Stable and Long-Term Transgene Expression in Fibroblasts for Syngeneic Mouse Tumor Models.International journal of molecular sciences · 2020Article
- RNA Virus-Based Episomal Vector with a Fail-Safe Switch Facilitating Efficient Genetic Modification and Differentiation of iPSCs.Molecular therapy. Methods & clinical development · 2019Article
- Human Genomic Safe Harbors and the Suicide Gene-Based Safeguard System for iPSC-Based Cell Therapy.Stem cells translational medicine · 2019Article
- Lentiviral transduction of mammalian cells for fast, scalable and high-level production of soluble and membrane proteins.Nature protocols · 2018Article
- Characterization of a core region in the A2UCOE that confers effective anti-silencing activity.Scientific reports · 2017Article
- The CpG-sites of the CBX3 ubiquitous chromatin opening element are critical structural determinants for the anti-silencing function.Scientific reports · 2017Article
- Engineering cell-based therapies to interface robustly with host physiology.Advanced drug delivery reviews · 2016Review
- A minimal ubiquitous chromatin opening element (UCOE) effectively prevents silencing of juxtaposed heterologous promoters by epigenetic remodeling in multipotent and pluripotent stem cells.Nucleic acids research · 2015Article
- DNA methylation and histone modifications are the molecular lock in lentivirally transduced hematopoietic progenitor cells.BioMed research international · 2015Article
- Ectopic DNMT3L triggers assembly of a repressive complex for retroviral silencing in somatic cells.Journal of virology · 2014Article
- Article
- Role of DNA methylation in expression and transmission of porcine endogenous retroviruses.Journal of virology · 2013Article
- Sustained knockdown of a disease-causing gene in patient-specific induced pluripotent stem cells using lentiviral vector-based gene therapy.Stem cells translational medicine · 2013Article
- Hepatic stem cell niches.The Journal of clinical investigation · 2013Review
- Retroviral DNA methylation and epigenetic repression are mediated by the antiviral host protein Daxx.Journal of virology · 2013Article
- A competitive cell growth assay for the detection of subtle effects of gene transduction on cell proliferation.Gene therapy · 2012Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Embryonic stem cells are subjected to a dynamic genome regulation during development. Here we report that the ectopic lentiviral transgenes are quickly silenced in murine embryonic carcinoma P19 cells. The silencing was correlated with CpG hypermethylation in the transgene promoter. Using high-resolution sodium bisulfite genome sequencing, we detected distinct DNA methylation kinetics in different proviral regions. DNase I sensitivity and chromatin immunoprecipitation assays revealed condensed chromatin structure and histone code switch during silencing. Longitudinal analysis of nonsilenced and silenced identical single-cell clones revealed that the silencing was coupled with CpG methylation in the promoter, as well as a global histone H3 deacetylation. Interestingly, the primer binding site and the packaging signal region appeared to serve as a DNA methylation initiation center which was rapidly hypermethylated regardless of transgene silencing and chromatin modifications. Analysis of cellular genes 45 to 50 kbp upstream and downstream of the integration site indicated that transcriptional activities of the flanking host genes were not affected. Genetic modifications of stem cells have great therapeutic potentials and our results picture a dynamic embryonic genome response to ectopic transgene integration that may have important implications in the future safety and efficacy modifications of stem cells.
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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.