ArticleEpigenetics & chromatin2010
Transcription-dependent silencing of inducible convergent transgenes in transgenic mice.
Article in Epigenetics & chromatin, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 35 citations in OpenAlex.
- Advancing in vivo reprogramming with synthetic biology.Current opinion in biotechnology · 2024Review
- The sound of silence: Transgene silencing in mammalian cell engineering.Cell systems · 2022Review
- Modeling Alzheimer's disease: considerations for a better translational and replicable mouse model.Neural regeneration research · 2022Article
- Acute and chronic effects of a light-activated FGF receptor in keratinocytes in vitro and in mice.Life science alliance · 2021Article
- Fluorescent PSC-Derived Cardiomyocyte Reporter Lines: Generation Approaches and Their Applications in Cardiovascular Medicine.Biology · 2020Review
- Article
- Unexpected effects of ivermectin and selamectin on inducible CreLaboratory animal research · 2020Article
- Functional Interrogation of a Depression-Related Serotonergic Single Nucleotide Polymorphism, rs6295, Using a Humanized Mouse Model.ACS chemical neuroscience · 2019Article
- Comparison of platelet-derived and plasma factor VIII efficacy using a novel native whole blood thrombin generation assay.Journal of thrombosis and haemostasis : JTH · 2015Article
- Sry-Independent Overexpression of Sox9 Supports Spermatogenesis and Fertility in the Mouse.Biology of reproduction · 2015Article
- RNAi-mediated gene silencing in zebrafish triggered by convergent transcription.Scientific reports · 2014Article
- Seeing is believing: visualizing transcriptional dynamics in single cells.Journal of cellular physiology · 2014Review
- RNA interference is responsible for reduction of transgene expression after Sleeping Beauty transposase mediated somatic integration.PloS one · 2012Article
- Gain of DNA methylation is enhanced in the absence of CTCF at the human retinoblastoma gene promoter.BMC cancer · 2011Article
- Vascular smooth muscle Jak2 deletion prevents angiotensin II-mediated neointima formation following injury in mice.Journal of molecular and cellular cardiology · 2011Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSilencing of transgenes in mice is a common phenomenon typically associated with short multi-copy transgenes. We have investigated the regulation of the highly inducible human granulocyte-macrophage colony-stimulating-factor gene (Csf2) in transgenic mice.
resultsIn the absence of any previous history of transcriptional activation, this transgene was expressed in T lineage cells at the correct inducible level in all lines of mice tested. In contrast, the transgene was silenced in a specific subset of lines in T cells that had encountered a previous episode of activation. Transgene silencing appeared to be both transcription-dependent and mediated by epigenetic mechanisms. Silencing was accompanied by loss of DNase I hypersensitive sites and inability to recruit RNA polymerase II upon stimulation. This pattern of silencing was reflected by increased methylation and decreased acetylation of histone H3 K9 in the transgene. We found that silenced lines were specifically associated with a single pair of tail-to-tail inverted repeated copies of the transgene embedded within a multi-copy array.
conclusionsOur study suggests that epigenetic transgene silencing can result from convergent transcription of inverted repeats which can lead to silencing of an entire multi-copy transgene array. This mechanism may account for a significant proportion of the reported cases of transgene inactivation in mice.
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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.