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Human zinc fingers as building blocks in the construction of artificial transcription factors
We describe methods for generating artificial transcription factors capable of up- or downregulating the expression of genes whose promoter regions contain the target DNA sequences. To accomplish this, we screened zinc fingers derived from sequences in the human genome and isolated 56 zinc fingers w...
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| Published in: | Nature biotechnology 2003-03, Vol.21 (3), p.275-280 |
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| Main Authors: | , , , , , , , , , , , , , , , , , |
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| cited_by | cdi_FETCH-LOGICAL-c626t-a9280ebbc01861e1c547b7f648448db5f64ffda779aab02875c7e0a393eb0fcf3 |
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| cites | cdi_FETCH-LOGICAL-c626t-a9280ebbc01861e1c547b7f648448db5f64ffda779aab02875c7e0a393eb0fcf3 |
| container_end_page | 280 |
| container_issue | 3 |
| container_start_page | 275 |
| container_title | Nature biotechnology |
| container_volume | 21 |
| creator | Kim, Jin-Soo Bae, Kwang-Hee Do Kwon, Young Shin, Hyun-Chul Hwang, Moon-Sun Ryu, Eun-Hyun Park, Kyung-Soon Yang, Hyo-Young Lee, Dong-ki Lee, Yangsoon Park, Jinwoo Sun Kwon, Heung Kim, Hyun-Won Yeh, Byung-Il Lee, Hyean-Woo Hyung Sohn, Soon Yoon, Joonho Seol, Wongi |
| description | We describe methods for generating artificial transcription factors capable of up- or downregulating the expression of genes whose promoter regions contain the target DNA sequences. To accomplish this, we screened zinc fingers derived from sequences in the human genome and isolated 56 zinc fingers with diverse DNA-binding specificities. We used these zinc fingers as modular building blocks in the construction of novel, sequence-specific DNA-binding proteins. Fusion of these zinc-finger proteins with either a transcriptional activation or repression domain yielded potent transcriptional activators or repressors, respectively. These results show that the human genome encodes zinc fingers with diverse DNA-binding specificities and that these domains can be used to design sequence-specific DNA-binding proteins and artificial transcription factors. |
| doi_str_mv | 10.1038/nbt796 |
| format | article |
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To accomplish this, we screened zinc fingers derived from sequences in the human genome and isolated 56 zinc fingers with diverse DNA-binding specificities. We used these zinc fingers as modular building blocks in the construction of novel, sequence-specific DNA-binding proteins. Fusion of these zinc-finger proteins with either a transcriptional activation or repression domain yielded potent transcriptional activators or repressors, respectively. These results show that the human genome encodes zinc fingers with diverse DNA-binding specificities and that these domains can be used to design sequence-specific DNA-binding proteins and artificial transcription factors.</description><identifier>ISSN: 1087-0156</identifier><identifier>EISSN: 1546-1696</identifier><identifier>DOI: 10.1038/nbt796</identifier><identifier>PMID: 12592413</identifier><identifier>CODEN: NABIF9</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Agriculture ; Amino acids ; Bioinformatics ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedical Engineering/Biotechnology ; Biomedicine ; Biotechnology ; Cloning ; Deoxyribonucleic acid ; DNA ; DNA - chemistry ; DNA - genetics ; DNA - metabolism ; DNA-Binding Proteins - biosynthesis ; DNA-Binding Proteins - chemistry ; DNA-Binding Proteins - genetics ; Fundamental and applied biological sciences. Psychology ; Gene Expression Regulation ; Genes ; Genetic engineering ; Genetic technics ; Genome, Human ; Genomes ; Humans ; Life Sciences ; Methods. Procedures. Technologies ; Modification of gene expression level ; Peptide Library ; Plasmids ; Prefabricated buildings ; Protein Engineering - methods ; Proteins ; Recombinant Proteins - chemistry ; Recombinant Proteins - genetics ; Recombinant Proteins - metabolism ; Transcription factors ; Transcription Factors - biosynthesis ; Transcription Factors - chemistry ; Transcription Factors - genetics ; Transcription, Genetic ; Yeast ; Yeasts - genetics ; Yeasts - metabolism ; Zinc ; Zinc Fingers - genetics</subject><ispartof>Nature biotechnology, 2003-03, Vol.21 (3), p.275-280</ispartof><rights>Springer Nature America, Inc. 2003</rights><rights>2003 INIST-CNRS</rights><rights>COPYRIGHT 2003 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Mar 2003</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c626t-a9280ebbc01861e1c547b7f648448db5f64ffda779aab02875c7e0a393eb0fcf3</citedby><cites>FETCH-LOGICAL-c626t-a9280ebbc01861e1c547b7f648448db5f64ffda779aab02875c7e0a393eb0fcf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2727,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14598140$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12592413$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Jin-Soo</creatorcontrib><creatorcontrib>Bae, Kwang-Hee</creatorcontrib><creatorcontrib>Do Kwon, Young</creatorcontrib><creatorcontrib>Shin, Hyun-Chul</creatorcontrib><creatorcontrib>Hwang, Moon-Sun</creatorcontrib><creatorcontrib>Ryu, Eun-Hyun</creatorcontrib><creatorcontrib>Park, Kyung-Soon</creatorcontrib><creatorcontrib>Yang, Hyo-Young</creatorcontrib><creatorcontrib>Lee, Dong-ki</creatorcontrib><creatorcontrib>Lee, Yangsoon</creatorcontrib><creatorcontrib>Park, Jinwoo</creatorcontrib><creatorcontrib>Sun Kwon, Heung</creatorcontrib><creatorcontrib>Kim, Hyun-Won</creatorcontrib><creatorcontrib>Yeh, Byung-Il</creatorcontrib><creatorcontrib>Lee, Hyean-Woo</creatorcontrib><creatorcontrib>Hyung Sohn, Soon</creatorcontrib><creatorcontrib>Yoon, Joonho</creatorcontrib><creatorcontrib>Seol, Wongi</creatorcontrib><title>Human zinc fingers as building blocks in the construction of artificial transcription factors</title><title>Nature biotechnology</title><addtitle>Nat Biotechnol</addtitle><addtitle>Nat Biotechnol</addtitle><description>We describe methods for generating artificial transcription factors capable of up- or downregulating the expression of genes whose promoter regions contain the target DNA sequences. To accomplish this, we screened zinc fingers derived from sequences in the human genome and isolated 56 zinc fingers with diverse DNA-binding specificities. We used these zinc fingers as modular building blocks in the construction of novel, sequence-specific DNA-binding proteins. Fusion of these zinc-finger proteins with either a transcriptional activation or repression domain yielded potent transcriptional activators or repressors, respectively. These results show that the human genome encodes zinc fingers with diverse DNA-binding specificities and that these domains can be used to design sequence-specific DNA-binding proteins and artificial transcription factors.</description><subject>Agriculture</subject><subject>Amino acids</subject><subject>Bioinformatics</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical Engineering/Biotechnology</subject><subject>Biomedicine</subject><subject>Biotechnology</subject><subject>Cloning</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA - chemistry</subject><subject>DNA - genetics</subject><subject>DNA - metabolism</subject><subject>DNA-Binding Proteins - biosynthesis</subject><subject>DNA-Binding Proteins - chemistry</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Regulation</subject><subject>Genes</subject><subject>Genetic engineering</subject><subject>Genetic technics</subject><subject>Genome, Human</subject><subject>Genomes</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Methods. Procedures. Technologies</subject><subject>Modification of gene expression level</subject><subject>Peptide Library</subject><subject>Plasmids</subject><subject>Prefabricated buildings</subject><subject>Protein Engineering - methods</subject><subject>Proteins</subject><subject>Recombinant Proteins - chemistry</subject><subject>Recombinant Proteins - genetics</subject><subject>Recombinant Proteins - metabolism</subject><subject>Transcription factors</subject><subject>Transcription Factors - biosynthesis</subject><subject>Transcription Factors - chemistry</subject><subject>Transcription Factors - genetics</subject><subject>Transcription, Genetic</subject><subject>Yeast</subject><subject>Yeasts - genetics</subject><subject>Yeasts - metabolism</subject><subject>Zinc</subject><subject>Zinc Fingers - genetics</subject><issn>1087-0156</issn><issn>1546-1696</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><recordid>eNqNkl2L1TAQhoso7of6C0SCoOJF16TNVy-XRd2FhQW_7qQkaXLM2ibHTAquv94cWzysXii5yCTzzIR38lbVI4JPCG7lq6Cz6Pid6pAwymvCO363xFiKGhPGD6ojgGuMMaec368OSMO6hpL2sPp8Pk8qoB8-GOR82NgESAHSsx-HckR6jOYrIB9Q_mKRiQFymk32MaDokErZO2-8GlFOKoBJfvsr55TJMcGD6p5TI9iH635cfXzz-sPZeX159fbi7PSyNrzhuVZdI7HV2mAiObHEMCq0cJxKSuWgWYmcG5QQnVIaN1IwIyxWbddajZ1x7XH1fOm7TfHbbCH3kwdjx1EFG2foRYsFZoT_EyRSNC2hO_DpH-B1nFMoIvqmwYRLJkSBThZoo0bb--BimYIpa7CTL7Oyzpf7U9IVXQ1rWSl4eaugMNl-zxs1A_QX79_9P3v16Ta7yjIpAiTr-m3yk0o3PcH9zh_94o8CPlllzXqywx5bDVGAZyugwKjRlV81HvYcZZ0kFBfuxcJBSe1ss5_PX08-Xsig8pzs71Zr-idiydgh</recordid><startdate>20030301</startdate><enddate>20030301</enddate><creator>Kim, Jin-Soo</creator><creator>Bae, Kwang-Hee</creator><creator>Do Kwon, Young</creator><creator>Shin, Hyun-Chul</creator><creator>Hwang, Moon-Sun</creator><creator>Ryu, Eun-Hyun</creator><creator>Park, Kyung-Soon</creator><creator>Yang, Hyo-Young</creator><creator>Lee, Dong-ki</creator><creator>Lee, Yangsoon</creator><creator>Park, Jinwoo</creator><creator>Sun Kwon, Heung</creator><creator>Kim, Hyun-Won</creator><creator>Yeh, Byung-Il</creator><creator>Lee, Hyean-Woo</creator><creator>Hyung Sohn, Soon</creator><creator>Yoon, Joonho</creator><creator>Seol, Wongi</creator><general>Nature Publishing Group US</general><general>Nature</general><general>Nature Publishing Group</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7P</scope><scope>M7S</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20030301</creationdate><title>Human zinc fingers as building blocks in the construction of artificial transcription factors</title><author>Kim, Jin-Soo ; Bae, Kwang-Hee ; Do Kwon, Young ; Shin, Hyun-Chul ; Hwang, Moon-Sun ; Ryu, Eun-Hyun ; Park, Kyung-Soon ; Yang, Hyo-Young ; Lee, Dong-ki ; Lee, Yangsoon ; Park, Jinwoo ; Sun Kwon, Heung ; Kim, Hyun-Won ; Yeh, Byung-Il ; Lee, Hyean-Woo ; Hyung Sohn, Soon ; Yoon, Joonho ; Seol, Wongi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c626t-a9280ebbc01861e1c547b7f648448db5f64ffda779aab02875c7e0a393eb0fcf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Agriculture</topic><topic>Amino acids</topic><topic>Bioinformatics</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedical Engineering/Biotechnology</topic><topic>Biomedicine</topic><topic>Biotechnology</topic><topic>Cloning</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA - chemistry</topic><topic>DNA - genetics</topic><topic>DNA - metabolism</topic><topic>DNA-Binding Proteins - biosynthesis</topic><topic>DNA-Binding Proteins - chemistry</topic><topic>DNA-Binding Proteins - genetics</topic><topic>Fundamental and applied biological sciences. 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To accomplish this, we screened zinc fingers derived from sequences in the human genome and isolated 56 zinc fingers with diverse DNA-binding specificities. We used these zinc fingers as modular building blocks in the construction of novel, sequence-specific DNA-binding proteins. Fusion of these zinc-finger proteins with either a transcriptional activation or repression domain yielded potent transcriptional activators or repressors, respectively. These results show that the human genome encodes zinc fingers with diverse DNA-binding specificities and that these domains can be used to design sequence-specific DNA-binding proteins and artificial transcription factors.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>12592413</pmid><doi>10.1038/nbt796</doi><tpages>6</tpages></addata></record> |
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| identifier | ISSN: 1087-0156 |
| ispartof | Nature biotechnology, 2003-03, Vol.21 (3), p.275-280 |
| issn | 1087-0156 1546-1696 |
| language | eng |
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| source | Nature |
| subjects | Agriculture Amino acids Bioinformatics Biological and medical sciences Biomedical and Life Sciences Biomedical Engineering/Biotechnology Biomedicine Biotechnology Cloning Deoxyribonucleic acid DNA DNA - chemistry DNA - genetics DNA - metabolism DNA-Binding Proteins - biosynthesis DNA-Binding Proteins - chemistry DNA-Binding Proteins - genetics Fundamental and applied biological sciences. Psychology Gene Expression Regulation Genes Genetic engineering Genetic technics Genome, Human Genomes Humans Life Sciences Methods. Procedures. Technologies Modification of gene expression level Peptide Library Plasmids Prefabricated buildings Protein Engineering - methods Proteins Recombinant Proteins - chemistry Recombinant Proteins - genetics Recombinant Proteins - metabolism Transcription factors Transcription Factors - biosynthesis Transcription Factors - chemistry Transcription Factors - genetics Transcription, Genetic Yeast Yeasts - genetics Yeasts - metabolism Zinc Zinc Fingers - genetics |
| title | Human zinc fingers as building blocks in the construction of artificial transcription factors |
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