ArticleMolecular therapy : the journal of the American Society of Gene Therapy2013
Kinetics and epigenetics of retroviral silencing in mouse embryonic stem cells defined by deletion of the D4Z4 element.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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.
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.
Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Nuclear compartmentalization at the G1/S transition plays a key role in DNA replication control.Nature communications · 2026Article
- Distinct metabolic dependency on BCAA defines cancer stemness and malignancy in human triple-negative breast cancer.Cell reports · 2026Article
- Insulated piggyBac and FRT vectors for engineering transgenic homozygous and heterozygous eHAP cells.Biology open · 2025Article
- Efficient generation of germline chimeras in a non-rodent species using rabbit induced pluripotent stem cells.Nature communications · 2025Article
- SHIELD: a platform for high-throughput screening of barrier-type DNA elements in human cells.Nature communications · 2023Article
- MeCP2 heterochromatin organization is modulated by arginine methylation and serine phosphorylation.Frontiers in cell and developmental biology · 2022Article
- Molecular Therapies for Muscular Dystrophies.Current treatment options in neurology · 2018Review
- Syngeneic Transplantation of Olfactory Ectomesenchymal Stem Cells Restores Learning and Memory Abilities in a Rat Model of Global Cerebral Ischemia.Stem cells international · 2018Article
- Detailed comparison of retroviral vectors and promoter configurations for stable and high transgene expression in human induced pluripotent stem cells.Gene therapy · 2017Article
- Dynamic silencing of somatic L1 retrotransposon insertions reflects the developmental and cellular contexts of their genomic integration.Mobile DNA · 2017Article
- LiPS-A3S, a human genomic site for robust expression of inserted transgenes.Molecular therapy. Nucleic acids · 2016Article
- Wnt/β-catenin signaling promotes self-renewal and inhibits the primed state transition in naïve human embryonic stem cells.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Targeting mRNA for the treatment of facioscapulohumeral muscular dystrophy.Intractable & rare diseases research · 2016Review
- Identification of the Drosophila X chromosome: The long and short of it.RNA biology · 2015Review
- Article
- Toward position-independent retroviral vector expression in pluripotent stem cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2013Article
Corrections and comments
- Commented on by
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Retroviral vectors are silenced in embryonic stem (ES) cells by epigenetic mechanisms whose kinetics are poorly understood. We show here that a 3'D4Z4 insulator directs retroviral expression with persistent but variable expression for up to 5 months. Combining an internal 3'D4Z4 with HS4 insulators in the long terminal repeats (LTRs) shows that these elements cooperate, and defines the first retroviral vector that fully escapes long-term silencing. Using FLP recombinase to induce deletion of 3'D4Z4 from the provirus in ES cell clones, we established retroviral silencing at many but not all integration sites. This finding shows that 3'D4Z4 does not target retrovirus integration into favorable epigenomic domains but rather protects the transgene from silencing. Chromatin analyses demonstrate that 3'D4Z4 blocks the spread of heterochromatin marks including DNA methylation and repressive histone modifications such as H3K9 methylation. In addition, our deletion system reveals three distinct kinetic classes of silencing (rapid, gradual or not silenced), in which multiple epigenetic pathways participate in silencing at different integration sites. We conclude that vectors with both 3'D4Z4 and HS4 insulator elements fully block silencing, and may have unprecedented utility for gene transfer applications that require long-term gene expression in pluripotent stem (PS) cells.
Indexed as
Identifiers
What OpenQuestion holds
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.