Cited by 2,488Bacterial Genetics and BiotechnologyGene Regulatory Network AnalysisCRISPR and Genetic Engineering

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Transcriptional Activation by Tetracyclines in Mammalian Cells

Gossen, Manfred, Freundlieb, Sabine, Bender, Gabriele, Müller, Gerhard, Hillen, Wolfgang, Bujard, Hermann·1995·Science

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Abstract

A transcriptional transactivator was developed that fuses the VP16 activation domain with a mutant Tet repressor from Escherichia coli. This transactivator requires certain tetracycline (Tc) derivatives for specific DNA binding. Thus, addition of doxycycline to HeLa cells that constitutively synthesized the transactivator and that contained an appropriate, stably integrated reporter unit rapidly induced gene expression more than a thousandfold. The specificity of the Tet repressor-operator-effector interaction and the pharmacological characteristics of Tc's make this regulatory system well suited for the control of gene activities in vivo, such as in transgenic animals and possibly in gene therapy.

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Tight control of gene expression in mammalian cells by tetracycline-responsive promoters.
Gossen, M., & Bujard, H. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.12.5547 · Cited by 4,943
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10.1016/0003-2697(87)90021-2 · DOI
10.1016/0003-2697(83)90418-9 · DOI
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Modulation of neuronal survival and axonal growth in vivo by tetracycline-regulated neurotrophin expression
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“2 mg), which expresses the tetracycline repressor/VP16 activator (49) used to regulate expression of the pTRE plasmid, was cotransfected with the pTRE-GFP-LXXLL or pTREGFP-a/bV expression vectors.”
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Highly Conserved RNA Sequences That Are Sensors of Environmental Stress
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Gene Therapy for Brain Tumors
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“One of these systems was devised by Gossen et al. (1995) (reviewed in Shockett and Schatz, 1996).”
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Two Novel Adenovirus Vector Systems Permitting Regulated Protein Expression in Gene Transfer Experiments
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“Transcription of the CAT reporter gene is activated by the addition of doxycycline (DOX) to the culture medium (4).”
BackgroundMethod
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“A reverse tetracycline-controlled transactivator rtTA has also been created by point mutating the tTA gene [57,92].”
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Method
Control of Erythropoietin Secretion by Doxycycline or Mifepristone in Mice Bearing Polymer-Encapsulated Engineered Cells
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BackgroundMethod
Murine Models of Acute Myeloid Leukaemia
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Background
Fast-acting and nearly gratuitous induction of gene expression and protein depletion in Saccharomyces cerevisiae
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Inducible expression of BCR/ABL using human CD34 regulatory elements results in a megakaryocytic myeloproliferative syndrome
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Bone Morphogenetic Protein Gene Therapy
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“This may be possible by the use of inducible promoters, which allow for the exogenous regulation of transgene expression using nontoxic, inert agents.(43,63) The most commonly used system is tetracycline based.”
Background
Down-regulation of endothelial cell growth inhibitors by enhanced MYCN oncogene expression in human neuroblastoma cells.
Fotsis, T., Breit, S., Lutz, W., Rössler, J., Hatzi, E., Schwab, M., & Schweigerer, L. (1999) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.1999.00575.x · Cited by 62
“3 molecules, and eliminate any possibility that this regulation was caused from additional genetic changes of long-term culture, we have used an inducible eukaryotic expression system based on the tetracycline repressor of Escherichia coli [21,22].”
Method
Use of tetracycline-controlled gene expression systems to study mammalian cell cycle.
Freundlieb, S., Baron, U., Bonin, A. L., Gossen, M., & Bujard, H. (1997) · Methods in Enzymology · doi:10.1016/s0076-6879(97)83014-5 · Cited by 62
Self-citation
Smart-watch-programmed green-light-operated percutaneous control of therapeutic transgenes
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“A “tet-on” system has been developed through engineering the reverse tetracycline transcriptional activator (rtTA) that binds tetO and activates gene transcription only in the presence of doxycycline (59, 105).”
Background
Herpes Simplex Virus Type 1 ICP27 Induces p38 Mitogen-Activated Protein Kinase Signaling and Apoptosis in HeLa Cells
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“We then transfected G418-resistant HTO cells, which are HeLa cells stably expressing the Tet-on transactivator ( 20 ), with pTE27 and a linear hygromycin resistance gene.”
BackgroundMethodInfluential
Conditional inhibition of cancer cell proliferation by tetracycline-responsive, H1 promoter-driven silencing of PLK1
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“We examined the dose–response for Dox, a Tet derivative, which was previously shown to be a very efficient effector for TetR (Gossen et al., 1995).”
Method
Demonstration of site-directed recombination in transgenic zebrafish using the Cre/loxP system
Pan, X., Wan, H., Chia, W., Tong, Y., & Gong, Z. (2005) · Transgenic research · doi:10.1007/s11248-004-5790-z · Cited by 61

Authors: Gossen, M., Freundlieb, S., Bender, G., Müller, G., Hillen, W., & Bujard, H.
Affiliations: Heidelberg University (DE)
ORCID: Gossen, Manfred
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1995-06-23
Volume: 268
Issue: 5218
Pages: 1766-1769
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.7792603
OpenAlex: W2005275397
Cited by: 2,488
References: 0
Citations by year: 2026: 31 · 2025: 43 · 2024: 45 · 2023: 49 · 2022: 55 · 2021: 60 · 2020: 68 · 2019: 52 · 2018: 55 · 2017: 47 · 2016: 52 · 2015: 62 · 2014: 53 · 2013: 67 · 2012: 64
FWCI: 48.56
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
Keywords: tetracycline, transcriptional activation, Tet repressor, VP16 activation domain, doxycycline, gene expression regulation, transcriptional activator, transgenic animals, gene therapy
MeSH terms: Amino Acid Sequence, Doxycycline, HeLa Cells, Humans, Molecular Sequence Data, Operator Regions, Genetic, Recombinant Fusion Proteins, Repressor Proteins, Transfection, Viral Proteins, Transcriptional Activation, Trans-Activators, Genes, Reporter, Simplexvirus

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Transcriptional Activation by Tetracyclines in Mammalian Cells

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