A tunable genetic switch based on RNAi and repressor proteins for regulating gene expression in mammalian cells
Here, we introduce an engineered, tunable genetic switch that couples repressor proteins and an RNAi target design to effectively turn any gene off. We used the switch to regulate the expression of EGFP in mouse and human cells and found that it offers >99% repression as well as the ability to tu...
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| Published in | Cell Vol. 130; no. 2; pp. 363 - 372 |
|---|---|
| Main Authors | , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
27.07.2007
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| Subjects | |
| Online Access | Get full text |
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| Abstract | Here, we introduce an engineered, tunable genetic switch that couples repressor proteins and an RNAi target design to effectively turn any gene off. We used the switch to regulate the expression of EGFP in mouse and human cells and found that it offers >99% repression as well as the ability to tune gene expression. To demonstrate the system's modularity and level of gene silencing, we used the switch to tightly regulate the expression of diphtheria toxin and Cre recombinase, respectively. We also used the switch to tune the expression of a proapoptotic gene and show that a threshold expression level is required to induce apoptosis. This work establishes a system for tight, tunable control of mammalian gene expression that can be used to explore the functional role of various genes as well as to determine whether a phenotype is the result of a threshold response to changes in gene expression. |
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| AbstractList | Here, we introduce an engineered, tunable genetic switch that couples repressor proteins and an RNAi target design to effectively turn any gene off. We used the switch to regulate the expression of EGFP in mouse and human cells and found that it offers >99% repression as well as the ability to tune gene expression. To demonstrate the system's modularity and level of gene silencing, we used the switch to tightly regulate the expression of diphtheria toxin and Cre recombinase, respectively. We also used the switch to tune the expression of a proapoptotic gene and show that a threshold expression level is required to induce apoptosis. This work establishes a system for tight, tunable control of mammalian gene expression that can be used to explore the functional role of various genes as well as to determine whether a phenotype is the result of a threshold response to changes in gene expression. |
| Author | Cantor, Charles R Collins, James J Deans, Tara L |
| Author_xml | – sequence: 1 givenname: Tara L surname: Deans fullname: Deans, Tara L organization: Department of Biomedical Engineering, Center for BioDynamics and Center for Advanced Biotechnology, Boston University, Boston, MA 02215, USA – sequence: 2 givenname: Charles R surname: Cantor fullname: Cantor, Charles R – sequence: 3 givenname: James J surname: Collins fullname: Collins, James J |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/17662949$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.1038/35888 10.1038/35002131 10.1038/nature03508 10.1016/S0022-2836(02)00994-4 10.1038/nmeth846 10.1073/pnas.1332628100 10.1038/nature02491 10.1016/0092-8674(87)90234-0 10.1073/pnas.0307571101 10.1126/science.1070919 10.1126/science.1106914 10.1038/35014651 10.1016/0092-8674(87)90536-8 10.1016/S0960-9822(07)00562-3 10.1038/nbt980 10.1016/j.cell.2006.07.025 10.1016/0092-8674(95)90082-9 10.1016/0092-8674(78)90099-5 10.1126/science.1109090 10.1074/jbc.273.13.7770 10.1073/pnas.80.22.6853 10.1073/pnas.0408507102 10.1073/pnas.0407218101 10.1016/S0092-8674(03)00346-5 10.1038/nature01546 10.1016/0022-2836(81)90375-2 10.1016/j.ymben.2005.02.005 10.1083/jcb.139.5.1281 10.1038/35002125 10.1016/j.jbiotec.2006.01.003 10.1038/ng869 10.1371/journal.pbio.0030064 10.1002/(SICI)1097-0320(19980101)31:1<1::AID-CYTO1>3.0.CO;2-R 10.1038/5007 10.1016/S1084-9521(02)00017-4 10.1158/1535-7163.MCT-06-0205 10.1158/1535-7163.207.4.2 10.1073/pnas.88.3.698 10.1038/sj.onc.1202966 10.1073/pnas.89.12.5547 10.1038/nature04473 10.1006/mthe.2002.0694 10.1073/pnas.0500345102 10.1038/nbt986 10.1073/pnas.0402940101 10.1126/science.1067407 10.1038/nature02370 |
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| References | Greenfield (10.1016/j.cell.2007.05.045_bib16) 1983; 80 Gossen (10.1016/j.cell.2007.05.045_bib15) 1992; 89 Becskei (10.1016/j.cell.2007.05.045_bib6) 2000; 405 Guido (10.1016/j.cell.2007.05.045_bib18) 2006; 439 Imai (10.1016/j.cell.2007.05.045_bib22) 2001; 98 Rosenfeld (10.1016/j.cell.2007.05.045_bib38) 2002; 323 Kobayashi (10.1016/j.cell.2007.05.045_bib27) 2004; 101 Soriano (10.1016/j.cell.2007.05.045_bib42) 1999; 21 Fung (10.1016/j.cell.2007.05.045_bib13) 2005; 435 Isaacs (10.1016/j.cell.2007.05.045_bib24) 2004; 22 van Engeland (10.1016/j.cell.2007.05.045_bib45) 1998; 31 Kramer (10.1016/j.cell.2007.05.045_bib30) 2005; 7 Malphettes (10.1016/j.cell.2007.05.045_bib31) 2006; 124 Elowitz (10.1016/j.cell.2007.05.045_bib10) 2000; 403 Isalan (10.1016/j.cell.2007.05.045_bib25) 2005; 3 Kramer (10.1016/j.cell.2007.05.045_bib28) 2005; 102 Ozbudak (10.1016/j.cell.2007.05.045_bib33) 2002; 31 Fire (10.1016/j.cell.2007.05.045_bib12) 1998; 391 Aneja (10.1016/j.cell.2007.05.045_bib2) 2006; 5 Kramer (10.1016/j.cell.2007.05.045_bib29) 2004; 22 Katiyar (10.1016/j.cell.2007.05.045_bib26) 2005; 4 Guo (10.1016/j.cell.2007.05.045_bib19) 1995; 81 Guet (10.1016/j.cell.2007.05.045_bib17) 2002; 296 Szulc (10.1016/j.cell.2007.05.045_bib44) 2006; 3 Isaacs (10.1016/j.cell.2007.05.045_bib23) 2003; 100 Basu (10.1016/j.cell.2007.05.045_bib5) 2004; 101 You (10.1016/j.cell.2007.05.045_bib48) 2004; 428 Danielian (10.1016/j.cell.2007.05.045_bib9) 1998; 8 Peng (10.1016/j.cell.2007.05.045_bib37) 2002; 6 Yamaizumi (10.1016/j.cell.2007.05.045_bib47) 1978; 15 Paddison (10.1016/j.cell.2007.05.045_bib34) 2004; 428 Elowitz (10.1016/j.cell.2007.05.045_bib11) 2002; 297 Shinoura (10.1016/j.cell.2007.05.045_bib41) 1999; 18 Blake (10.1016/j.cell.2007.05.045_bib7) 2003; 422 Brown (10.1016/j.cell.2007.05.045_bib8) 1987; 49 Hooshangi (10.1016/j.cell.2007.05.045_bib20) 2005; 102 Banaszynski (10.1016/j.cell.2007.05.045_bib4) 2006; 126 Ornitz (10.1016/j.cell.2007.05.045_bib32) 1991; 88 Scrable (10.1016/j.cell.2007.05.045_bib40) 2002; 13 Hu (10.1016/j.cell.2007.05.045_bib21) 1987; 48 Pedraza (10.1016/j.cell.2007.05.045_bib36) 2005; 307 Rosenfeld (10.1016/j.cell.2007.05.045_bib39) 2005; 307 Anderson (10.1016/j.cell.2007.05.045_bib1) 2004; 101 Gardner (10.1016/j.cell.2007.05.045_bib14) 2000; 403 Sternberg (10.1016/j.cell.2007.05.045_bib43) 1981; 150 Pastorino (10.1016/j.cell.2007.05.045_bib35) 1998; 273 Wolter (10.1016/j.cell.2007.05.045_bib46) 1997; 139 Atkinson (10.1016/j.cell.2007.05.045_bib3) 2003; 113 |
| References_xml | – volume: 391 start-page: 806 year: 1998 ident: 10.1016/j.cell.2007.05.045_bib12 article-title: Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans publication-title: Nature doi: 10.1038/35888 contributor: fullname: Fire – volume: 403 start-page: 339 year: 2000 ident: 10.1016/j.cell.2007.05.045_bib14 article-title: Construction of a genetic toggle switch in Escherichia coli publication-title: Nature doi: 10.1038/35002131 contributor: fullname: Gardner – volume: 435 start-page: 118 year: 2005 ident: 10.1016/j.cell.2007.05.045_bib13 article-title: A synthetic gene-metabolic oscillator publication-title: Nature doi: 10.1038/nature03508 contributor: fullname: Fung – volume: 323 start-page: 785 year: 2002 ident: 10.1016/j.cell.2007.05.045_bib38 article-title: Negative autoregulation speeds the response times of transcription networks publication-title: J. Mol. Biol. doi: 10.1016/S0022-2836(02)00994-4 contributor: fullname: Rosenfeld – volume: 98 start-page: 224 year: 2001 ident: 10.1016/j.cell.2007.05.045_bib22 article-title: Impaired adipogenesis and lipolysis in the mouse upon selective ablation of the retinoid X receptor alpha mediated by a tamoxifen-inducible chimeric Cre recombinase (Cre-ERT2) in adipocytes publication-title: Proc. Natl. Acad. Sci. USA contributor: fullname: Imai – volume: 3 start-page: 109 year: 2006 ident: 10.1016/j.cell.2007.05.045_bib44 article-title: A versatile tool for conditional gene expression and knockdown publication-title: Nat. Methods doi: 10.1038/nmeth846 contributor: fullname: Szulc – volume: 100 start-page: 7714 year: 2003 ident: 10.1016/j.cell.2007.05.045_bib23 article-title: Prediction and measurement of an autoregulatory genetic module publication-title: Proc. Natl. Acad. Sci. USA doi: 10.1073/pnas.1332628100 contributor: fullname: Isaacs – volume: 428 start-page: 868 year: 2004 ident: 10.1016/j.cell.2007.05.045_bib48 article-title: Programmed population control by cell-cell communication and regulated killing publication-title: Nature doi: 10.1038/nature02491 contributor: fullname: You – volume: 48 start-page: 555 year: 1987 ident: 10.1016/j.cell.2007.05.045_bib21 article-title: The inducible lac operator-repressor system is functional in mammalian cells publication-title: Cell doi: 10.1016/0092-8674(87)90234-0 contributor: fullname: Hu – volume: 101 start-page: 6355 year: 2004 ident: 10.1016/j.cell.2007.05.045_bib5 article-title: Spatiotemporal control of gene expression with pulse-generating networks publication-title: Proc. Natl. Acad. Sci. USA doi: 10.1073/pnas.0307571101 contributor: fullname: Basu – volume: 297 start-page: 1183 year: 2002 ident: 10.1016/j.cell.2007.05.045_bib11 article-title: Stochastic gene expression in a single cell publication-title: Science doi: 10.1126/science.1070919 contributor: fullname: Elowitz – volume: 307 start-page: 1962 year: 2005 ident: 10.1016/j.cell.2007.05.045_bib39 article-title: Gene regulation at the single-cell level publication-title: Science doi: 10.1126/science.1106914 contributor: fullname: Rosenfeld – volume: 405 start-page: 590 year: 2000 ident: 10.1016/j.cell.2007.05.045_bib6 article-title: Engineering stability in gene networks by autoregulation publication-title: Nature doi: 10.1038/35014651 contributor: fullname: Becskei – volume: 49 start-page: 603 year: 1987 ident: 10.1016/j.cell.2007.05.045_bib8 article-title: lac repressor can regulate expression from a hybrid SV40 early promoter containing a lac operator in animal cells publication-title: Cell doi: 10.1016/0092-8674(87)90536-8 contributor: fullname: Brown – volume: 8 start-page: 1323 year: 1998 ident: 10.1016/j.cell.2007.05.045_bib9 article-title: Modification of gene activity in mouse embryos in utero by a tamoxifen-inducible form of Cre recombinase publication-title: Curr. Biol. doi: 10.1016/S0960-9822(07)00562-3 contributor: fullname: Danielian – volume: 22 start-page: 867 year: 2004 ident: 10.1016/j.cell.2007.05.045_bib29 article-title: An engineered epigenetic transgene switch in mammalian cells publication-title: Nat. Biotechnol. doi: 10.1038/nbt980 contributor: fullname: Kramer – volume: 126 start-page: 995 year: 2006 ident: 10.1016/j.cell.2007.05.045_bib4 article-title: A rapid, reversible, and tunable method to regulate protein function in living cells using synthetic small molecules publication-title: Cell doi: 10.1016/j.cell.2006.07.025 contributor: fullname: Banaszynski – volume: 81 start-page: 611 year: 1995 ident: 10.1016/j.cell.2007.05.045_bib19 article-title: par-1, a gene required for establishing polarity in C. elegans embryos, encodes a putative Ser/Thr kinase that is asymmetrically distributed publication-title: Cell doi: 10.1016/0092-8674(95)90082-9 contributor: fullname: Guo – volume: 15 start-page: 245 year: 1978 ident: 10.1016/j.cell.2007.05.045_bib47 article-title: One molecule of diphtheria toxin fragment A introduced into a cell can kill the cell publication-title: Cell doi: 10.1016/0092-8674(78)90099-5 contributor: fullname: Yamaizumi – volume: 307 start-page: 1965 year: 2005 ident: 10.1016/j.cell.2007.05.045_bib36 article-title: Noise propagation in gene networks publication-title: Science doi: 10.1126/science.1109090 contributor: fullname: Pedraza – volume: 273 start-page: 7770 year: 1998 ident: 10.1016/j.cell.2007.05.045_bib35 article-title: The overexpression of Bax produces cell death upon induction of the mitochondrial permeability transition publication-title: J. Biol. Chem. doi: 10.1074/jbc.273.13.7770 contributor: fullname: Pastorino – volume: 80 start-page: 6853 year: 1983 ident: 10.1016/j.cell.2007.05.045_bib16 article-title: Nucleotide sequence of the structural gene for diphtheria toxin carried by corynebacteriophage beta publication-title: Proc. Natl. Acad. Sci. USA doi: 10.1073/pnas.80.22.6853 contributor: fullname: Greenfield – volume: 102 start-page: 3581 year: 2005 ident: 10.1016/j.cell.2007.05.045_bib20 article-title: Ultrasensitivity and noise propagation in a synthetic transcriptional cascade publication-title: Proc. Natl. Acad. Sci. USA doi: 10.1073/pnas.0408507102 contributor: fullname: Hooshangi – volume: 101 start-page: 16028 year: 2004 ident: 10.1016/j.cell.2007.05.045_bib1 article-title: A polymer library approach to suicide gene therapy for cancer publication-title: Proc. Natl. Acad. Sci. USA doi: 10.1073/pnas.0407218101 contributor: fullname: Anderson – volume: 113 start-page: 597 year: 2003 ident: 10.1016/j.cell.2007.05.045_bib3 article-title: Development of genetic circuitry exhibiting toggle switch or oscillatory behavior in Escherichia coli publication-title: Cell doi: 10.1016/S0092-8674(03)00346-5 contributor: fullname: Atkinson – volume: 422 start-page: 633 year: 2003 ident: 10.1016/j.cell.2007.05.045_bib7 article-title: Noise in eukaryotic gene expression publication-title: Nature doi: 10.1038/nature01546 contributor: fullname: Blake – volume: 150 start-page: 467 year: 1981 ident: 10.1016/j.cell.2007.05.045_bib43 article-title: Bacteriophage P1 site-specific recombination. I. Recombination between loxP sites publication-title: J. Mol. Biol. doi: 10.1016/0022-2836(81)90375-2 contributor: fullname: Sternberg – volume: 7 start-page: 241 year: 2005 ident: 10.1016/j.cell.2007.05.045_bib30 article-title: Semi-synthetic mammalian gene regulatory networks publication-title: Metab. Eng. doi: 10.1016/j.ymben.2005.02.005 contributor: fullname: Kramer – volume: 139 start-page: 1281 year: 1997 ident: 10.1016/j.cell.2007.05.045_bib46 article-title: Movement of Bax from the cytosol to mitochondria during apoptosis publication-title: J. Cell Biol. doi: 10.1083/jcb.139.5.1281 contributor: fullname: Wolter – volume: 403 start-page: 335 year: 2000 ident: 10.1016/j.cell.2007.05.045_bib10 article-title: A synthetic oscillatory network of transcriptional regulators publication-title: Nature doi: 10.1038/35002125 contributor: fullname: Elowitz – volume: 124 start-page: 732 year: 2006 ident: 10.1016/j.cell.2007.05.045_bib31 article-title: Improved transgene expression fine-tuning in mammalian cells using a novel transcription-translation network publication-title: J. Biotechnol. doi: 10.1016/j.jbiotec.2006.01.003 contributor: fullname: Malphettes – volume: 31 start-page: 69 year: 2002 ident: 10.1016/j.cell.2007.05.045_bib33 article-title: Regulation of noise in the expression of a single gene publication-title: Nat. Genet. doi: 10.1038/ng869 contributor: fullname: Ozbudak – volume: 3 start-page: e64 year: 2005 ident: 10.1016/j.cell.2007.05.045_bib25 article-title: Engineering gene networks to emulate Drosophila embryonic pattern formation publication-title: PLoS Biol. doi: 10.1371/journal.pbio.0030064 contributor: fullname: Isalan – volume: 31 start-page: 1 year: 1998 ident: 10.1016/j.cell.2007.05.045_bib45 article-title: Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure publication-title: Cytometry doi: 10.1002/(SICI)1097-0320(19980101)31:1<1::AID-CYTO1>3.0.CO;2-R contributor: fullname: van Engeland – volume: 21 start-page: 70 year: 1999 ident: 10.1016/j.cell.2007.05.045_bib42 article-title: Generalized lacZ expression with the ROSA26 Cre reporter strain publication-title: Nat. Genet. doi: 10.1038/5007 contributor: fullname: Soriano – volume: 13 start-page: 109 year: 2002 ident: 10.1016/j.cell.2007.05.045_bib40 article-title: Say when: reversible control of gene expression in the mouse by lac publication-title: Semin. Cell Dev. Biol. doi: 10.1016/S1084-9521(02)00017-4 contributor: fullname: Scrable – volume: 5 start-page: 2366 year: 2006 ident: 10.1016/j.cell.2007.05.045_bib2 article-title: Treatment of hormone-refractory breast cancer: apoptosis and regression of human tumors implanted in mice publication-title: Mol. Cancer Ther. doi: 10.1158/1535-7163.MCT-06-0205 contributor: fullname: Aneja – volume: 4 start-page: 207 year: 2005 ident: 10.1016/j.cell.2007.05.045_bib26 article-title: Silymarin induces apoptosis primarily through a p53-dependent pathway involving Bcl-2/Bax, cytochrome c release, and caspase activation publication-title: Mol. Cancer Ther. doi: 10.1158/1535-7163.207.4.2 contributor: fullname: Katiyar – volume: 88 start-page: 698 year: 1991 ident: 10.1016/j.cell.2007.05.045_bib32 article-title: Binary system for regulating transgene expression in mice: targeting int-2 gene expression with yeast GAL4/UAS control elements publication-title: Proc. Natl. Acad. Sci. USA doi: 10.1073/pnas.88.3.698 contributor: fullname: Ornitz – volume: 18 start-page: 5703 year: 1999 ident: 10.1016/j.cell.2007.05.045_bib41 article-title: Relative level of expression of Bax and Bcl-XL determines the cellular fate of apoptosis/necrosis induced by the overexpression of Bax publication-title: Oncogene doi: 10.1038/sj.onc.1202966 contributor: fullname: Shinoura – volume: 89 start-page: 5547 year: 1992 ident: 10.1016/j.cell.2007.05.045_bib15 article-title: Tight control of gene expression in mammalian cells by tetracycline-responsive promoters publication-title: Proc. Natl. Acad. Sci. USA doi: 10.1073/pnas.89.12.5547 contributor: fullname: Gossen – volume: 439 start-page: 856 year: 2006 ident: 10.1016/j.cell.2007.05.045_bib18 article-title: A bottom-up approach to gene regulation publication-title: Nature doi: 10.1038/nature04473 contributor: fullname: Guido – volume: 6 start-page: 537 year: 2002 ident: 10.1016/j.cell.2007.05.045_bib37 article-title: Regulated expression of diphtheria toxin in prostate cancer cells publication-title: Mol. Ther. doi: 10.1006/mthe.2002.0694 contributor: fullname: Peng – volume: 102 start-page: 9517 year: 2005 ident: 10.1016/j.cell.2007.05.045_bib28 article-title: Hysteresis in a synthetic mammalian gene network publication-title: Proc. Natl. Acad. Sci. USA doi: 10.1073/pnas.0500345102 contributor: fullname: Kramer – volume: 22 start-page: 841 year: 2004 ident: 10.1016/j.cell.2007.05.045_bib24 article-title: Engineered riboregulators enable post-transcriptional control of gene expression publication-title: Nat. Biotechnol. doi: 10.1038/nbt986 contributor: fullname: Isaacs – volume: 101 start-page: 8414 year: 2004 ident: 10.1016/j.cell.2007.05.045_bib27 article-title: Programmable cells: interfacing natural and engineered gene networks publication-title: Proc. Natl. Acad. Sci. USA doi: 10.1073/pnas.0402940101 contributor: fullname: Kobayashi – volume: 296 start-page: 1466 year: 2002 ident: 10.1016/j.cell.2007.05.045_bib17 article-title: Combinatorial synthesis of genetic networks publication-title: Science doi: 10.1126/science.1067407 contributor: fullname: Guet – volume: 428 start-page: 427 year: 2004 ident: 10.1016/j.cell.2007.05.045_bib34 article-title: A resource for large-scale RNA-interference-based screens in mammals publication-title: Nature doi: 10.1038/nature02370 contributor: fullname: Paddison |
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| SubjectTerms | Animals Apoptosis bcl-2-Associated X Protein - metabolism Cell Line CHO Cells Cricetinae Cricetulus Diphtheria Toxin - metabolism Gene Regulatory Networks Genes, Switch Humans Integrases - metabolism Mice Repressor Proteins - metabolism RNA Interference |
| Title | A tunable genetic switch based on RNAi and repressor proteins for regulating gene expression in mammalian cells |
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