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

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Transcriptional Activation by Tetracyclines in Mammalian Cells

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

Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.1126/science.7792603

Cites

0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

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
Self-citation

Flagged first, then by citations

Show all 0 references

Research works printed but not linked: 13

10.1016/0003-2697(87)90021-2 · DOI
10.1016/0003-2697(83)90418-9 · DOI
FURTH, P.A., TEMPORAL CONTROL OF GENE-EXPRESSION IN TRANSGENIC MICE BY A TETRACYCLINE-RESPONSIVE PROMOTER, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 91: 9302 (1994).
GOSSEN, M, CONTROL OF GENE ACTIVITY IN HIGHER EUKARYOTIC CELLS BY PROKARYOTIC REGULATORY ELEMENTS, TRENDS IN BIOCHEMICAL SCIENCES 18: 471 (1993). · DOI
HECHT, B, NONINDUCIBLE TET REPRESSOR MUTATIONS MAP FROM THE OPERATOR BINDING MOTIF TO THE C-TERMINUS, JOURNAL OF BACTERIOLOGY 175: 1206 (1993). · DOI
HILLEN, W, MECHANISMS UNDERLYING EXPRESSION OF TN10 ENCODED TETRACYCLINE RESISTANCE, ANNUAL REVIEW OF MICROBIOLOGY 48: 345 (1994). · DOI · Paper page
HINRICHS, W, STRUCTURE OF THE TET REPRESSOR TETRACYCLINE COMPLEX AND REGULATION OF ANTIBIOTIC-RESISTANCE, SCIENCE 264: 418 (1994). · DOI · Paper page
MULLER G THESIS U ERLANGEN NU (1995).
RESNITZKY, D, ACCELERATION OF THE G(1)/S PHASE-TRANSITION BY EXPRESSION OF CYCLIN-D1 AND CYCLIN-E WITH AN INDUCIBLE SYSTEM, MOLECULAR AND CELLULAR BIOLOGY 14: 1669 (1994).
10.1073/pnas.81.7.1991 · DOI
SOUTHERN, P.J., J MOL APPL GENET 1: 327 (1982).
WEINMANN, P, A CHIMERIC TRANSACTIVATOR ALLOWS TETRACYCLINE-RESPONSIVE GENE-EXPRESSION IN WHOLE PLANTS, PLANT JOURNAL 5: 559 (1994). · DOI
YARRANTON, G.T., CURR OPIN BIOTECH 3: 506 (1992). · DOI

Sorted by citations

Items 701–800 of 1,006

A predictable ligand regulated expression strategy for stably integrated transgenes in mammalian cells in culture.
Anastassiadis, K., Kim, J., Daigle, N., Sprengel, R., Schöler, H., & Stewart, A. (2002) · Gene · doi:10.1016/s0378-1119(02)00979-4 · Cited by 51
Regulation of Adenovirus-Mediated Elafin Transgene Expression by Bacterial Lipopolysaccharide
Simpson, A., Cunningham, G. A., Porteous, D. J., Haslett, C., & Sallenave, J. (2001) · Human Gene Therapy · doi:10.1089/104303401750298553 · Cited by 51
“Therefore, our data add the mCMV promoter to the growing list of promoters that can be activated selectively during inflammation or induced using exogenous activators (Gossen et al. , 1995; Varley et al. , 1995; No et al. , 1996).”
Conditional Transgene Expression in Endothelial Cells
Sarao, R., & Dumont, D. (1998) · Transgenic research · doi:10.1023/a:1008837410485 · Cited by 51
Advances in gene targeting methods.
Kuehn, R., & Schwenk, F. (1997) · Current Opinion in Immunology · doi:10.1016/s0952-7915(97)80133-1 · Cited by 51
Modulation of Erythropoietin Delivery from Engineered Muscles in Mice
Bohl, D., & Heard, J. (1997) · Human Gene Therapy · doi:10.1089/hum.1997.8.2-195 · Cited by 51
Long-term Cre-mediated retrograde tagging of neurons using a novel recombinant pseudorabies virus
Oyibo, H. K., Znamenskiy, P., Oviedo, H. V., Enquist, L. W., & Zador, A. M. (2014) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2014.00086 · Cited by 51
“We made a cell line with the reverse tetracycline-controlled transactivator (rtTA) and then inserted a transgene under the control of the tetracycling-inducible promoter, pTRE (promoter tetracycline response element) (Gossen et al., 1995).”
BackgroundMethod
Gene therapy approaches to enhancing plasticity and regeneration after spinal cord injury
Franz, S., Weidner, N., & Blesch, A. (2011) · Experimental Neurology · doi:10.1016/j.expneurol.2011.01.015 · Cited by 48
Facilitation of fatty acid uptake by CD36 in insulin-producing cells reduces fatty-acid-induced insulin secretion and glucose regulation of fatty acid oxidation
Wallin, T., Ma, Z., Ogata, H., Jørgensen, I. H., Iezzi, M., Wang, H., Wollheim, C. B., & Björklund, A. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2009.11.002 · Cited by 48
Conditional RNAi: towards a silent gene therapy.
Lee, S.-K., & Kumar, P. (2009) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2009.03.016 · Cited by 50
Contemporary approaches for modifying the mouse genome
Adams, D. J., & van der Weyden, L. (2008) · Physiological Genomics · doi:10.1152/physiolgenomics.90242.2008 · Cited by 42
Regulation of the Dha Operon of Lactococcus lactis
Christen, S., Srinivas, A., Bähler, P., Zeller, A., Pridmore, D., Bieniossek, C., Baumann, U., & Erni, B. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m603486200 · Cited by 50
Angiopoietin 1 prevents retinal detachment in an aggressive model of proliferative retinopathy, but has no effect on established neovascularization
Nambu, H., Umeda, N., Kachi, S., Oshima, Y., Akiyama, H., Nambu, R., & Campochiaro, P. A. (2005) · Journal of Cellular Physiology · doi:10.1002/jcp.20292 · Cited by 51
“…in which a tissue-specific or ubiquitous promoter drives expression of the reverse tetracycyline transactivator (rtTA), a transcription factor that binds to the tetracycline response element (TRE) only in the presence of tetracycline or the tetracycline analog, doxycycline (Gossen et al., 1995).”
Background
IGFBP-3 mediates p53-induced apoptosis during serum starvation
Grimberg, A., Liu, B.-R., Bannerman, P. G. C., El‐Deiry, W. S., & Cohen, P. (2002) · International Journal of Oncology · doi:10.3892/ijo.21.2.327 · Cited by 47
Correction of Hyperglycemia in Diabetic Mice Transplanted with Reversibly Immortalized Pancreatic β Cells Controlled by the tet-on Regulatory System
Milo-Landesman, D., Surana, M., Berkovich, I., Compagni, A., Christofori, G., Fleischer, N., & Efrat, S. (2001) · Cell Transplantation · doi:10.3727/000000001783986422 · Cited by 50
The C-terminal domain of the Bloom syndrome DNA helicase is essential for genomic stability
Yankiwski, V., Noonan, J. P., & Neff, N. F. (2001) · BMC Cell Biology · doi:10.1186/1471-2121-2-11 · Cited by 45
“An SV40-transformed BS cell line (GM0855B) was transfected with a plasmid containing an expression unit for the tetracycline or doxycycline (Tet) responsive transcriptional transactivator [32].”
Method
High-Titer Recombinant Adeno-Associated Virus Production from Replicating Amplicons and Herpes Vectors Deleted for Glycoprotein H
Zhang, X., de Alwis, M., Hart, S. L., Fitzke, F. W., Inglis, S. C., Boursnell, M. E. G., Levinsky, R. J., Kinnon, C., Ali, R. R., & Thrasher, A. J. (1999) · Human Gene Therapy · doi:10.1089/10430349950016861 · Cited by 48
“In this study, chromosomally integrated vector and packaging sequences, both incorporating the SV40 origin, could be amplified by expression of SV40 large T antigen under the con-trol of a reverse tetracycline trans-activator (Gossen et al. , 1995).”
HLA-A*0201-restricted cytolytic responses to the rtTA transactivator dominant and cryptic epitopes compromise transgene expression induced by the tetracycline on system
Ginhoux, F., Turbant, S., Gross, D. A., Poupiot, J., Marais, T., Lone, Y., Lemonnier, F. A., Firat, H., Perez, N., Danos, O., et al. (2004) · Molecular Therapy · doi:10.1016/j.ymthe.2004.05.012 · Cited by 49
A Multiplex MoClo Toolkit for Extensive and Flexible Engineering of Saccharomyces cerevisiae
Shaw, W. M., Khalil, A. S., & Ellis, T. (2023) · ACS Synthetic Biology · doi:10.1021/acssynbio.3c00423 · Cited by 49
Autonomous push button–controlled rapid insulin release from a piezoelectrically activated subcutaneous cell implant
Zhao, H., Xue, S., Hussherr, M., Teixeira, A. P., & Fussenegger, M. (2022) · Science Advances · doi:10.1126/sciadv.abm4389 · Cited by 52
Versatile approach for functional analysis of human proteins and efficient stable cell line generation using FLP-mediated recombination system
Szczęsny, R. J., Kowalska, K. J., Kłosowska-Kosicka, K., Chlebowski, A., Owczarek, E. P., Warkocki, Z., Kuliński, T. M., Adamska, D., Affek, K., Jędroszkowiak, A., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0194887 · Cited by 59
A role for activated Cdc42 in glioblastoma multiforme invasion
Okura, H., Golbourn, B., Shahzad, U., Agnihotri, S., Sabha, N., Krieger, J., Figueiredo, C. A., Chalil, A., Landon-Brace, N., Riemenschneider, A. N., et al. (2016) · OncoTarget · doi:10.18632/oncotarget.10925 · Cited by 49
“Briefly, the Cdc42 open reading frame was cloned into the pLVXTet3G vector via BamHI and NotI sites and packaged into lentiviruses [50].”
Gene therapy to treat cardiac arrhythmias
Bongianino, R., & Priori, S. G. (2015) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2015.61 · Cited by 55
PLZF/ZBTB16, a glucocorticoid response gene in acute lymphoblastic leukemia, interferes with glucocorticoid-induced apoptosis
Wasim, M., Carlet, M., Mansha, M., Greil, R., Ploner, C., Trockenbacher, A., Rainer, J., & Kofler, R. (2010) · Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2010.04.019 · Cited by 49
Construction and characterization of new piggyBac vectors for constitutive or inducible expression of heterologous gene pairs and the identification of a previously unrecognized activator sequence in piggyBac
Shi, X., Harrison, R. L., Hollister, J., Mohammed, A., Fraser, M. J. J., & Jarvis, D. (2007) · BMC Biotechnology · doi:10.1186/1472-6750-7-5 · Cited by 49
“A transcriptional control element consisting of back-toback minimal cytomegalovirus immediate early promoters (PCMVmin) separated by a tetracycline-inducible operator (TetO7; [32]) was constructed in several steps (Fig.”
Background
Controlling the kinetics of transgene expression by plasmid design
Yew, N. S. (2005) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2004.12.009 · Cited by 43
Autophagy‐dependent cell survival and cell death in an autosomal dominant familial neurohypophyseal diabetes insipidus in vitro model
Castino, R., Isidoro, C., & Murphy, D. (2005) · The FASEB Journal · doi:10.1096/fj.04-3163fje · Cited by 49
“Ad-VCAT-Cys67stop encodes the Cys67stop truncated VP precursor and is implicated as the cause of adFNDI in a Japanese family (21), under the control of the tetracycline-responsive element (TRE) (32).”
Background
Molecular mechanisms of learning and memory
Dunning, J., & During, M. J. (2003) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399403006707 · Cited by 39
Development of genetically engineered tet HPV16-E6/E7 transduced human corneal epithelial clones having tight regulation of proliferation and normal differentiation.
Mohan, R., Possin, D., Mohan, R., Sinhá, S., & Wilson, S. (2003) · Experimental Eye Research · doi:10.1016/s0014-4835(03)00175-1 · Cited by 49
Idiopathic Pulmonary Fibrosis
Kaminski, N., Belperio, J. A., Bitterman, P. B., Chen, L., Chensue, S. W., Choi, A. M. K., Đačić, S., Dauber, J. H., du Bois, R. M., Enghild, J. J., et al. (2003) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2003-0159su · Cited by 62
Natural antisense (rTSalpha) RNA induces site-specific cleavage of thymidylate synthase mRNA.
Chu, J., & Dolnick, B. (2002) · Biochimica et Biophysica Acta · doi:10.1016/s0925-4439(02)00081-9 · Cited by 49
Getting around lethality with inducible Cre-mediated excision
Garcia, E. L., & Mills, A. A. (2002) · Seminars in Cell and Developmental Biology · doi:10.1016/s1084-9521(02)00019-8 · Cited by 37
Understanding hypertension through genetic manipulation in mice.
Cvetkovic, B., & Sigmund, C. D. (2000) · Kidney International · doi:10.1046/j.1523-1755.2000.057003863.x · Cited by 49
“Recent modification of this system also allows its use as an activator of gene expressio”
Method
Development of a tetracycline controlled gene expression system in the parasitic protozoan Giardia lamblia.
Sun, C.-H., & Tai, J.-H. (2000) · Molecular and biochemical parasitology (Print) · doi:10.1016/s0166-6851(99)00163-2 · Cited by 49
Regulated expression of the Shiga toxin B gene induces apoptosis in mammalian fibroblastic cells
Nakagawa, I., Nakata, M., Kawabata, S., & Hamada, S. (1999) · Molecular Microbiology · doi:10.1046/j.1365-2958.1999.01564.x · Cited by 49
“Establishment of tetracycline-inducible Stx gene expression cells For analysis of the cytoplasmic function of the Stx subunits, a tetracycline-controlled gene expression system was used (Gossen et al., 1995; Paulus et al., 1997).”
BackgroundMethod
Immune-privileged tissues formed from immunologically cloaked mouse embryonic stem cells survive long term in allogeneic hosts
Harding, J., Vintersten-Nagy, K., Yang, H., Tang, J., Shutova, M., Jong, E., Lee, J.-H., Massumi, M., Oussenko, T., Izadifar, Z., et al. (2023) · Nature Biomedical Engineering · doi:10.1038/s41551-023-01133-y · Cited by 48
Natural promoters and promoter engineering strategies for metabolic regulation in Saccharomyces cerevisiae
He, S., Zhang, Z., & Lu, W.-Y. (2023) · Journal of Industrial Microbiology & Biotechnology · doi:10.1093/jimb/kuac029 · Cited by 48
Lineage-specific function of the noncoding Tsix RNA for Xist repression and Xi reactivation in micePreprint
Ohhata, T., Senner, C. E., Hemberger, M., & Wutz, A. (2011) · Genes & Development · doi:10.1101/gad.16997911 · Cited by 45
“We generated an inducible Tsix allele in mice taking advantage of the tetracycline-regulated expression system (Gossen et al. 1995).”
Method
Molecular Mechanisms of Astrogliosis
Correa-Cerro, L. S., & Mandell, J. W. (2007) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/01.jnen.0000248555.53079.d5 · Cited by 43
“Astrocyte-Specific Tetracycline-Regulated Transgenics Tetracycline-regulatable gene expression systems have been in use for over a decade (48, 49).”
Background
Sox10‐rtTA mouse line for tetracycline‐inducible expression of transgenes in neural crest cells and oligodendrocytes
Ludwig, A., Schlierf, B., Schardt, A., Nave, K., & Wegner, M. (2004) · Genesis · doi:10.1002/gene.20083 · Cited by 48
“…high-mobility group; Tet-on; Schwann cell; melanocyte; enteric nervous system Conditional knockout strategies are often based on the Cre-loxP technology or the Tet-system in which gene expression can be turned on or turned off upon treatment with doxycycline (Gossen et al., 1995; Lewandoski, 2001).”
Background
Hypoxia Inducible Double Plasmid System for Myocardial Ischemia Gene Therapy
Tang, Y., Jackson, M., Qian, K.-P., & Phillips, M. (2002) · HYPERTENSION · doi:10.1161/hy0202.103784 · Cited by 48
A novel tetracycline-dependent transactivator with E2F4 transcriptional activation domain.
Akagi, K., Kanai, M., Saya, H., Kozu, T., & Berns, A. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.4.e23 · Cited by 48
“A BamHI site was introduced at the stop codon of the reverse-type tetracycline repressor gene ( 2 ) by PCR (primer: 5′-GACCTC-CATAGAAGACAC-3′ ,5 ′-CGCGGATCCACTTTCACATT-3′) and the PCR product was digested with EcoRI and BamHI.”
BackgroundMethodInfluential
Systemic linear polyethylenimine (L-PEI)-mediated gene delivery in the mouse
Zou, S., Erbacher, P., Rémy, J.-S., & Behr, J. (2000) · The Journal of Gene Medicine · doi:10.1002/(sici)1521-2254(200003/04)2:2 · Cited by 317
A tunable dual-input system for on-demand dynamic gene expression regulation
Pedone, E., Postiglione, L., Aulicino, F., Rocca, D. L., Montes-Olivas, S., Khazim, M., di Bernardo, D., Cosma, M. P., & Marucci, L. (2019) · Nature Communications · doi:10.1038/s41467-019-12329-9 · Cited by 53
Non-degradative Ubiquitination of Protein Kinases
Ball, K. A., Johnson, J. R., Lewinski, M. K., Guatelli, J., Verschueren, E., Krogan, N. J., & Jacobson, M. P. (2016) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1004898 · Cited by 43
“For ubiquitination analysis in HEK293 cells, a HEK293 cell line was engineered to express HIV (strain NL4-3) with a tetracycline-responsive promoter element using the pTRE-Tight TetOn system (Clontech) [86] and a self-inactivating deletion in the 3’UTR to prevent second round infection (publication forthcoming).”
Method
Synthetic biology: new strategies for directing design.
Lynch, S. A., & Gill, R. (2012) · Metabolic Engineering · doi:10.1016/j.ymben.2011.12.007 · Cited by 47
Development of an inducible suicide gene system based on human caspase 8
Carlotti, F., Zaldumbide, A., Martin, P., Boulukos, K., Hoeben, R., & Pognonec, P. (2005) · Cancer Gene Therapy · doi:10.1038/sj.cgt.7700825 · Cited by 47
“15 We also investigated the ability of two widely used transcriptional regulatory systems, the Tet-On system”
Method
Rapid and simple determination of doxycycline in serum by high-performance liquid chromatography. Application to particulate drug delivery systems.
Ruz, N., Zabala, M., Kramer, M., Campanero, M., Dios-Viéitez, M., & Blanco-Prı́eto, M. J. (2004) · Journal of Chromatography A · doi:10.1016/j.chroma.2003.12.028 · Cited by 47
Nip21 Gene Expression Reduces Coxsackievirus B3 Replication by Promoting Apoptotic Cell Death via a Mitochondria-Dependent Pathway
Zhang, H., Yanagawa, B., Cheung, P., Luo, H.-L., Yuan, J., Chau, D., Wang, A.-K., Bohunek, L., Wilson, J. E., McManus, B., et al. (2002) · Circulation Research · doi:10.1161/01.res.0000024690.69379.5c · Cited by 47
The p75 Neurotrophin Receptor (p75NTR) Alters Tumor Necrosis Factor-mediated NF-κB Activity under Physiological Conditions, but Direct p75NTR-mediated NF-κB Activation Requires Cell Stress*
Bhakar, A., Roux, P. P., Lachance, C., Kryl, D., Zeindler, C., & Barker, P. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.30.21443 · Cited by 47
Integration complexes derived from HIV vectors for rapid assays in vitro
Hansen, M., Smith, G. J. I., Kafri, T., Molteni, V., Siegel, J., & Bushman, F. (1999) · Nature Biotechnology · doi:10.1038/9886 · Cited by 47
“The fourth construction encoded tetracycline transactivator (tTA), an inducible transcriptional activator that controls the activity of parts 1 and 2”
Background
Micronuclei formation and aneuploidy induced by Vpr, an accessory gene of human immunodeficiency virus type 1
Shimura, M., Tanaka, Y., Nakamura, S., Minemoto, Y., Yamashita, K., Hatake, K., Takaku, F., & Ishizaka, Y. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.6.621 · Cited by 47
“Plasmids for the reverse-tet system (41) were from Dr.”
Method
Genetically Encoded Toolbox for Glycocalyx Engineering: Tunable Control of Cell Adhesion, Survival, and Cancer Cell Behaviors
Shurer, C. R., Colville, M. J., Gupta, V. K., Head, S. E., Kai, F., Lakins, J. N., & Paszek, M. J. (2017) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.7b00037 · Cited by 59
Scalable Production in Human Cells and Biochemical Characterization of Full-Length Normal and Mutant Huntingtin
Huang, B., Lucas, T., Kueppers, C., Dong, X.-M., Krause, M., Bepperling, A., Buchner, J., Voshol, H., Weiss, A., Gerrits, B., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0121055 · Cited by 46
Broadly Applicable Methodology for the Rapid and Dosable Small Molecule-Mediated Regulation of Transcription Factors in Human Cells
Shoulders, M. D., Ryno, L. M., Cooley, C. B., Kelly, J. W., & Wiseman, R. L. (2013) · Journal of the American Chemical Society · doi:10.1021/ja402756p · Cited by 42
Functional Effects of GRM1 Suppression in Human Melanoma Cells
Wangari-Talbot, J., Wall, B., Goydos, J. S., & Chen, S. (2012) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-12-0158 · Cited by 46
“The tetracycline operon–based, tetracycline-inducible system (7, 23, 24) and the nonmammalian steroid–based, ecdysone-inducible system (15, 16, 25) have been shown to be both reversible and efficient in regulating the expression of various mammalian genes.”
Background
Nuclear Hormone Retinoid X Receptor (RXR) Negatively Regulates the Glucose-Stimulated Insulin Secretion of Pancreatic β-Cells
Miyazaki, S., Taniguchi, H., Moritoh, Y., Tashiro, F., Yamamoto, T., Yamato, E., Ikegami, H., Ozato, K., & Miyazaki, J. (2010) · Diabetes · doi:10.2337/db09-1897 · Cited by 46
Mammalian synthetic biology – from tools to therapies
Aubel, D., & Fussenegger, M. (2010) · BioEssays · doi:10.1002/bies.200900149 · Cited by 46
“With them, a panoply of mammalian transcription control systems has been engineered that are responsive to antibiotics,((18,27,28,29)) hormones and hormone analogs,((30,31,32)) quorum-sensing substances,((33)) and immunosuppressive and antidiabetic drugs.”
Background
A protein functional leap: how a single mutation reverses the function of the transcription regulator TetR
Resch, M., Striegl, H., Henssler, E.-M., Sevvana, M., Egerer-Sieber, C., Schiltz, E., Hillen, W., & Muller, Y. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn400 · Cited by 46
Self-citation
Regulation of insulin gene transcription by the immediate-early growth response gene Egr-1.
Eto, K., Kaur, V., & Thomas, M. K. (2006) · Endocrinology · doi:10.1210/en.2005-1336 · Cited by 46
A genetic redox sensor for mammalian cells.
Weber, W., Link, N., & Fussenegger, M. (2006) · Metabolic Engineering · doi:10.1016/j.ymben.2005.12.004 · Cited by 46
Control of small inhibitory RNA levels and RNA interference by doxycycline induced activation of a minimal RNA polymerase III promoter
Amar, L., Desclaux, M., Faucon‐Biguet, N., Mallet, J., & Vogel, R. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl034 · Cited by 46
“Indeed, the responsiveness to Dox was similar to that of the Tetdependent regulatory system which, by using rtTA as a transactivator, requires a Dox concentration of 1 mg/ml to induce the expression of transgenes in vitro (29).”
Approaches for trigger-inducible viral transgene regulation in gene-based tissue engineering.
Weber, W., & Fussenegger, M. (2004) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2004.07.003 · Cited by 46
Analysis of gene function in the zebrafish retina.
Malicki, J., Jo, H., Wei, X.-Y., Hsiung, M., & Pujic, Z. (2002) · Methods · doi:10.1016/s1046-2023(02)00262-1 · Cited by 46
Induced expression of melittin, an antimicrobial peptide, inhibits infection by Chlamydia trachomatis and Mycoplasma hominis in a HeLa cell line.
Lazarev, V., Parfenova, T. M., Gularyan, S. K., Misyurina, O. Y., Akopian, T., & Govorun, V. M. (2002) · International Journal of Antimicrobial Agents · doi:10.1016/s0924-8579(01)00479-4 · Cited by 46
Dual-regulated expression technology: a new era in the adjustment of heterologous gene expression in mammalian cells
Moser, S., Rimann, M., Fux, C., Schlatter, S., Bailey, J. E., & Fussenegger, M. (2001) · The Journal of Gene Medicine · doi:10.1002/jgm.219 · Cited by 48
“, submitted pGEM7Zf-Mek1DD Expression vector containing the constitutively active Mek1 double mutant, Mek1DD [38] pSEAP2-basic Vector containing the human secreted alkaline phosphatase (SEAP) Clontech pECFP-C1 Vector containing the enhanced cyan fluorescent protein Clontech pUHD15-1 Vector containing the tetracycline-…”
BackgroundMethodInfluential
In vitro selection of allosteric ribozymes: theory and experimental validation.
Piganeau, N., Thuillier, V., & Famulok, M. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.4981 · Cited by 46
“Controlling the expression of a gene offers a broad range of potential applications, both in research and for clinical purposes.(2) First, modulating the level of gene expression is an effective way to study its function.”
Inhibition of heat shock transcription factor by GR.
Wadekar, S., Li, D.-P., Periyasamy, S., & Sánchez, E. R. (2001) · Molecular Endocrinology · doi:10.1210/mend.15.8.0674 · Cited by 46
“This vector was cotransfected into the p2500-CAT-containing LHSE cells, along with the pUHD172–1hygro vector expressing the “reverse tet” transcriptional activator and hygromycin resistance genes, as originally developed by Bujard and co-workers (29).”
Method
Ras/MEK signaling suppresses Myc-dependent apoptosis in cells transformed by c-myc and activated ras
Tsuneoka, M., & Mekada, E. (2000) · Oncogene · doi:10.1038/sj.onc.1203232 · Cited by 46
“The v-ras gene was expressed under a doxycycline stimulated promoter (Gossen et al., 1995).”
BackgroundMethodInfluential
Overactivation of Phospholipase C-γ1 Renders Platelet-derived Growth Factor β-Receptor-expressing Cells Independent of the Phosphatidylinositol 3-Kinase Pathway for Chemotaxis*
Rönnstrand, L., Siegbahn, A., Rorsman, C., Johnell, M., Hansen, K., & Heldin, C. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.31.22089 · Cited by 46
Noninfectious Gene Transfer and Expression Systems for Cancer Gene Therapy
Cooper, M. J. (2002) · Elsevier eBooks · doi:10.1016/b978-012437551-2/50003-3 · Cited by 48
Genetic-code-expanded cell-based therapy for treating diabetes in mice
Chen, C., Yu, G., Huang, Y., Cheng, W., Li, Y., Sun, Y. X., Ye, H., & Liu, T. (2021) · Nature Chemical Biology · doi:10.1038/s41589-021-00899-z · Cited by 51
Selective toxicity of antibacterial agents—still a valid concept or do we miss chances and ignore risks?
Dalhoff, A. (2020) · Infection · doi:10.1007/s15010-020-01536-y · Cited by 60
Exploiting natural chemical photosensitivity of anhydrotetracycline and tetracycline for dynamic and setpoint chemo-optogenetic control
Baumschlager, A., Rullán, M., & Khammash, M. (2020) · Nature Communications · doi:10.1038/s41467-020-17677-5 · Cited by 45
Excess of NPM-ALK oncogenic signaling promotes cellular apoptosis and drug dependency
Ceccon, M., Merlo, M. E. B., Mologni, L., Poggio, T., Varesio, L. M., Menotti, M., Bombelli, S., Rigolio, R., Manazza, A. D., Giacomo, F. D., et al. (2015) · Oncogene · doi:10.1038/onc.2015.456 · Cited by 54
“54 For cell-sorting enrichment, cells were induced with 1 μ g/ml doxycycline hyciclate for 12 h and sorted for GFP expression on a MoFlo High-Performance Cell Sorter (Dako Cytomation, Carpinteria, CA, USA).”
Transgene Regulation Using the Tetracycline-Inducible TetR-KRAB System after AAV-Mediated Gene Transfer in Rodents and Nonhuman Primates
Guiner, C. L., Stieger, K., Toromanoff, A., Guilbaud, M., Mendes-Madeira, A., Devaux, M., Guigand, L., Chérel, Y., Moullier, P., Rolling, F., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0102538 · Cited by 50
“doxycycline (Dox) or rapamycin [7,8,9,10,11,12] for the two most”
Background
Vimentin Is Involved in Peptidylarginine Deiminase 2-Induced Apoptosis of Activated Jurkat Cells
Hsu, P.-C., Liao, Y.-L., Lin, C.-L., Lin, W.-H., Liu, G.-Y., & Hung, H.-C. (2014) · Molecules and Cells · doi:10.14348/molcells.2014.2359 · Cited by 45
“PADI2 overexpression induces apoptosis in activated Jurkat cells We generated a cell line that overexpressed the PADI2 transgene from a tetracycline-inducible promoter in an otherwise isogenic background (Gossen et al., 1995).”
Background
Impact of N-tau on adult hippocampal neurogenesis, anxiety, and memory
Pristerà, A., Saraulli, D., Vecchioli, S. F., Strimpakos, G., Costanzi, M., Certo, M. G. D., Cannas, S., Ciotti, M. T., Tirone, F., Mattei, E., et al. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.05.010 · Cited by 39
“To generate TRE-N-tau mice, the 1.3-Kb fragmentdcontaining 7 copies of TRE promoter, followed by the minimal cytomegalovirus promoter , the N-tau sequence and the SV40 poly(A)dwas excised from the pTRE-N-tau vector by NruI/BseRI digestion and used for microinjecting zygotes derived from hormonally primed 6-to 8- week-…”
Influential
Quantitative and simultaneous translational control of distinct mammalian mRNAs
Endo, K., Stapleton, J. A., Hayashi, K., Saito, H., & Inoue, T. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt347 · Cited by 40
“The concentration of the supplement determines the activity of the factors (8,9), each of which can evenly adjust the transcription levels of multiple target genes in a cell (Figure 1A).”
Background
Apoptosis pathways and oncolytic adenoviral vectors: promising targets and tools to overcome therapy resistance of malignant melanoma
Eberle, J., Fecker, L. F., Hossini, A. M., Kurbanov, B. M., & Fechner, H. (2007) · Experimental Dermatology · doi:10.1111/j.1600-0625.2007.00655.x · Cited by 42
Peroxisome proliferator-activated receptor alpha activation during pregnancy severely impairs mammary lobuloalveolar development in mice.
Yang, Q., Kurotani, R., Yamada, A., Kimura, S., & Gonzalez, F. (2006) · Endocrinology · doi:10.1210/en.2006-0437 · Cited by 45
Liver-specific expression of interferon γ following adenoviral gene transfer controls hepatitis B virus replication in mice
Dumortier, J., Schönig, K., Oberwinkler, H., Löw, R., Giese, T., Bujard, H., Schirmacher, P., & Protzer, U. (2005) · Gene Therapy · doi:10.1038/sj.gt.3302449 · Cited by 44
Self-citation
A New Hybrid System Capable of Efficient Lentiviral Vector Production and Stable Gene Transfer Mediated by a Single Helper-Dependent Adenoviral Vector
Kubo, S., & Mitani, K. (2003) · Journal of Virology · doi:10.1128/jvi.77.5.2964-2971.2003 · Cited by 39
“inducible transcriptional regulator (18) into our vector to produce LVs that can be regulated.”
Background
Toward Autologous ex Vivo Gene Therapy for the Central Nervous System with Human Adult Astrocytes
Ridet, J., Corti, O., Pencalet, P., Hanoun, N., Hamon, M., Philippon, J., & Mallet, J. (1999) · Human Gene Therapy · doi:10.1089/10430349950019057 · Cited by 45
“The gene regulatory system based on tetracycline (Gossen and Bu-jard, 1992; Gossen et al ., 1995) allows stringent control of gene activity in animals and effectively regulates foreign genes in the CNS (Corti et al ., 1996; Kistner et al ., 1996; Mayford et al ., 1996; Yu et al ., 1996; Saez et al…”
Transgenic animal models: new avenues in cardiovascular physiology
Franz, W.-M., Mueller, O. J., Hartong, R., Frey, N., & Katus, H. A. (1997) · Journal of Molecular Medicine · doi:10.1007/s001090050096 · Cited by 44
“Bujard and coworkers [ 112 ] have recently succeeded in engineering a hybrid transcription factor with a reversed dependency on tet for DNA binding.”
Background
Fast large-scale purification of tetracycline repressor variants from overproducing Escherichia coli strains.
Ettner, N., Müller, G., Berens, C., Backes, H., Schnappinger, D., Schreppel, T., Pfleiderer, K., & Hillen, W. (1996) · Journal of Chromatography A · doi:10.1016/0021-9673(96)00232-4 · Cited by 45
Self-citation
The Power of Reversibility
Schönig, K., Bujard, H., & Gossen, M. (2010) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(10)77022-1 · Cited by 41
Self-citation
Lighting up yeast cell factories by transcription factor-based biosensors
D’Ambrosio, V., & Jensen, M. K. (2017) · FEMS Yeast Research · doi:10.1093/femsyr/fox076 · Cited by 45
“ence of tetracycline or doxycycline, was later developed through randommutagenesis (Gossen et al. 1995) (Fig.”
Background
Synthetic biology devices and circuits for RNA-based ‘smart vaccines’: a propositional review
Andries, O., Kitada, T., Bodner, K., Sanders, N. N., & Weiss, R. (2015) · Expert Review of Vaccines · doi:10.1586/14760584.2015.997714 · Cited by 50
“, tetracycline-controlled transactivator: tTA [65] and reverse tetracycline-controlled transactivator: rtTA [66]) are arguably the most commonly used regulatory devices for creating synthetic gene circuits on DNA.”
Background
A novel pair of inducible expression vectors for use in Methylobacterium extorquens
Chubiz, L. M., Purswani, J., Carroll, S. M., & Marx, C. J. (2013) · BMC Research Notes · doi:10.1186/1756-0500-6-183 · Cited by 42
“In fact, TetR and related transcriptional repressors have found use in numerous synthetic biology applications in bacteria, archaea, and eukaryotes [13,18-23].”
Background
Gene transfer in tissue repair: status, challenges and future directions
Eming, S., Krieg, T., & Davidson, J. (2004) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.4.9.1373 · Cited by 44
“Furthermore, multiple regulatory systems have been developed, including the tetracycline-inducible system [75,76], the ecdysone (an insect steroid) inducible system [77], the RU486/ anti-progestin mifepristone-inducible system [78,79], and the rapamycin-inducible system [80].”
Background
Inhibition of established collagen-induced arthritis with a tumour necrosis factor-α inhibitor expressed from a self-contained doxycycline regulated plasmid
Gould, D., Bright, C., & Chernajovsky, Y. (2003) · Arthritis Research & Therapy · doi:10.1186/ar1036 · Cited by 44
“Principal among the transcriptionally regulated systems that have been developed are the tetracycline ‘off’ [11], ‘on’ [12] and ‘repressor’ [13] systems, and the ecdysone [14], rapamycin [15] and streptogramin [16] systems, which are all two- or three-component systems that utilize a small molecule to regulate the act…”
Background
Vectors for the treatment of autoimmune disease
Gould, D., & Favorov, P. (2003) · Gene Therapy · doi:10.1038/sj.gt.3302018 · Cited by 43
The p65 domain from NF-kappaB is an efficient human activator in the tetracycline-regulatable gene expression system.
Urlinger, S., Helbl, V., Guthmann, J., Pook, E., Grimm, S., & Hillen, W. (2000) · Gene · doi:10.1016/s0378-1119(00)00112-8 · Cited by 44
Self-citation
Highly controlled gene expression using combinations of a tissue-specific promoter, recombinant adenovirus and a tetracycline-regulatable transcription factor
Ghersa, P., Gobert, R. P., Sattonnet-Roche, P., Richards, C., Pich, E., & van Huijsduijnen, R. H. (1998) · Gene Therapy · doi:10.1038/sj.gt.3300713 · Cited by 44
TAXI/UAS: A Molecular Switch to Control Expression of Genes In Vivo
Delort, J., & Capecchi, M. R. (1996) · Human Gene Therapy · doi:10.1089/hum.1996.7.7-809 · Cited by 44
“This do main has been used extensively to confer n-ani-activator prop erties on inactive DNA-binding polypeptides (Sadowski et al, 1988; Elliston et al, 1990; Baim et al, 1991; Christopherson et al, 1992; White et al, 1992; Gilbert et al, 1993; Gossen et al, 1995).”
A piggyBac-based toolkit for inducible genome editing in mammalian cells
Schertzer, M. D., Thulson, E., Braceros, K. C., Lee, D. M., Hinkle, E. R., Murphy, R. M., Kim, S. O., Vitucci, E., & Calabrese, J. M. (2018) · bioRxiv · doi:10.1261/rna.068932.118 · Cited by 43
“…two separate piggyBac cargo vectors, one that expresses an inducible Cas9 or dCas9 variant, and another that expresses an sgRNA and the reverse-tetracycline transactivator [rtTA; (Gossen et al., 1995)], are transfected into cells along with a plasmid that expresses the piggyBac transposase.”
Background
Cell-based Analysis of Structure-Function Activity of Threonine Aspartase 1*
Bier, C., Knauer, S., Klapthor, A., Schweitzer, A., Rekik, A., Krämer, O., Marschalek, R., & Stauber, R. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.161646 · Cited by 43
Efficient integration of transgenes into a defined locus in human embryonic stem cells
Sakurai, K., Shimoji, M., Tahimic, C., Aiba, K., Kawase, E., Hasegawa, K., Amagai, Y., Suemori, H., & Nakatsuji, N. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkp1234 · Cited by 43
“Using this approach, we integrated a tetracycline (Tet)-inducible reporter and successfully introduced all components of the Tet-On system (15) into a defined site at the HPRT locus.”
Method
Viral vector approaches to modify gene expression in the brain
Papale, A., Cerovic, M., & Brambilla, R. (2009) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2009.08.013 · Cited by 41
TRIB3 is implicated in glucotoxicity- and oestrogen receptor-stress-induced β-cell apoptosis
Qian, B., Wang, H., Men, X., Zhang, W., Cai, H., Xu, S., Xu, Y., Ye, L., Wollheim, C. B., & Lou, J. (2008) · Journal of Endocrinology · doi:10.1677/joe-08-0331 · Cited by 52
“The INS rb cells were cotransfected with plasmids PUHD10-3 (Gossen et al. 1995), carrying rat TRIB3, and a plasmid pTK-hygro containing the hygromycin-resistance marker.”
Method

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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Transcriptional Activation by Tetracyclines in Mammalian Cells

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Metadata

Record

About these checks