ArticleNucleic acids research2017
Controlled re-activation of epigenetically silenced Tet promoter-driven transgene expression by targeted demethylation.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
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- Dicer is essential for proper maturation, composition, and function in the postnatal retina.iScience · 2025Article
- Reversing transgene silencing via targeted chromatin editing.bioRxiv : the preprint server for biology · 2025Article
- Programming megakaryocytes to produce engineered platelets for delivering non-native proteins.Communications biology · 2025Article
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- Advancing in vivo reprogramming with synthetic biology.Current opinion in biotechnology · 2024Review
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- An Update on Reported Variants in the Skeletal MuscleHuman mutation · 2024Review
- Overcoming the Silencing of Doxycycline-Inducible Promoters in hiPSC-derived Cardiomyocytes.Open research Europe · 2024Article
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- TET (Ten-eleven translocation) family proteins: structure, biological functions and applications.Signal transduction and targeted therapy · 2023Review
- Tetracycline-Inducible and Reversible Stable Gene Expression in Human iPSC-Derived Neural Progenitors and in the Postnatal Mouse Brain.Current protocols · 2023Article
- A Ubiquitous Chromatin Opening Element and DNA Demethylation Facilitate Doxycycline-Controlled Expression during Differentiation and in Transgenic Mice.ACS synthetic biology · 2023Article
- The non-catalytic role of DNA polymerase epsilon in replication initiation in human cells.Nature communications · 2022Article
- A Flp-dependent G-CaMP9a transgenic mouse for neuronal imagingCell reports methods · 2022Article
- Review
- Using recombinase-mediated cassette exchange to engineer MIN6 insulin-secreting cells based on a newly identified safe harbor locus.Journal of diabetes investigation · 2021Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Faithful expression of transgenes in cell cultures and mice is often challenged by locus dependent epigenetic silencing. We investigated silencing of Tet-controlled expression cassettes within the mouse ROSA26 locus. We observed pronounced DNA methylation of the Tet promoter concomitant with loss of expression in mES cells as well as in differentiated cells and transgenic animals. Strikingly, the ROSA26 promoter remains active and methylation free indicating that this silencing mechanism specifically affects the transgene, but does not spread to the host's chromosomal neighborhood. To reactivate Tet cassettes a synthetic fusion protein was constructed and expressed in silenced cells. This protein includes the enzymatic domains of ten eleven translocation methylcytosine dioxygenase 1 (TET-1) as well as the Tet repressor DNA binding domain. Expression of the synthetic fusion protein and Doxycycline treatment allowed targeted demethylation of the Tet promoter in the ROSA26 locus and in another genomic site, rescuing transgene expression in cells and transgenic mice. Thus, inducible, reversible and site-specific epigenetic modulation is a promising strategy for reactivation of silenced transgene expression, independent of the integration site.
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