ArticleNucleic acids research2015
A minimal ubiquitous chromatin opening element (UCOE) effectively prevents silencing of juxtaposed heterologous promoters by epigenetic remodeling in multipotent and pluripotent stem cells.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 90 citations in OpenAlex.
- Minimal CBX3-Derived UCOE Confers Long-Term Resistance to Transgene Silencing in Human iPSCs During Neuronal Differentiation.International journal of molecular sciences · 2026Article
- UCOE-Mediated Transcriptional Stabilization Combined with EGFP-Based FACS Screening Enables Efficient Selection of High-Producing CHO Cells.Molecular biotechnology · 2026Article
- Induction of human pruriceptors from pluripotent stem cells via transcription factors.Stem cell reports · 2026Article
- AAV Vectors in Regenerative Medicine and Cellular Reprogramming: Potential, Pitfalls, and Specificity Constraints.International journal of molecular sciences · 2026Review
- Lentiviral rescue of UMPS auxotrophy enables drug-free selection and stable vector expression.Molecular therapy. Advances · 2026Article
- Lights up on the embryonic dance: tools and applications of optogenetics in developmental biology.Genes & development · 2026Review
- One-step induction of human GABAergic neurons promotes presynaptic development & synapse maturation.bioRxiv : the preprint server for biology · 2025Article
- Reduced Cas9 transgene silencing by incorporation of intron sequences.Nature communications · 2025Article
- XPRESSO: Rapid genetic engineering of human pluripotent stem cells for durable overexpression using a modular anti-silencing vector.Stem cell reports · 2025Article
- Termination sequence between an inducible promoter and ubiquitous chromatin opening element (UCOE) reduces gene expression leakage and silencing.Journal of biological engineering · 2025Article
- Gene editing enables non-invasiveMolecular therapy. Methods & clinical development · 2025Article
- Barriers Composed of tRNA Genes Can Complement the Benefits of a Ubiquitous Chromatin Opening Element to Enhance Transgene Expression.Biotechnology journal · 2025Article
- Development and characterization of a first-in-class adjustable-dose gene therapy system.Gene · 2024Article
- Dynamical and combinatorial coding by MAPK p38 and NFκB in the inflammatory response of macrophages.Molecular systems biology · 2024Article
- Ultrasound-mediated gene delivery specifically targets liver sinusoidal endothelial cells for sustained FVIII expression in hemophilia A mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Overcoming the Silencing of Doxycycline-Inducible Promoters in hiPSC-derived Cardiomyocytes.Open research Europe · 2024Article
- Scalable generation of functional human iPSC-derived CAR-macrophages that efficiently eradicate CD19-positive leukemia.Journal for immunotherapy of cancer · 2023Article
- SHIELD: a platform for high-throughput screening of barrier-type DNA elements in human cells.Nature communications · 2023Article
- Stable expression of large transgenes via the knock-in of an integrase-deficient lentivirus.Nature biomedical engineering · 2023Article
- A Ubiquitous Chromatin Opening Element and DNA Demethylation Facilitate Doxycycline-Controlled Expression during Differentiation and in Transgenic Mice.ACS synthetic biology · 2023Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epigenetic silencing of transgene expression represents a major obstacle for the efficient genetic modification of multipotent and pluripotent stem cells. We and others have demonstrated that a 1.5 kb methylation-free CpG island from the human HNRPA2B1-CBX3 housekeeping genes (A2UCOE) effectively prevents transgene silencing and variegation in cell lines, multipotent and pluripotent stem cells, and their differentiated progeny. However, the bidirectional promoter activity of this element may disturb expression of neighboring genes. Furthermore, the epigenetic basis underlying the anti-silencing effect of the UCOE on juxtaposed promoters has been only partially explored. In this study we removed the HNRPA2B1 moiety from the A2UCOE and demonstrate efficient anti-silencing properties also for a minimal 0.7 kb element containing merely the CBX3 promoter. This DNA element largely prevents silencing of viral and tissue-specific promoters in multipotent and pluripotent stem cells. The protective activity of CBX3 was associated with reduced promoter CpG-methylation, decreased levels of repressive and increased levels of active histone marks. Moreover, the anti-silencing effect of CBX3 was locally restricted and when linked to tissue-specific promoters did not activate transcription in off target cells. Thus, CBX3 is a highly attractive element for sustained, tissue-specific and copy-number dependent transgene expression in vitro and in vivo.
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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.