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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Bibliographic Details
Published in:Nature biotechnology 2003-03, Vol.21 (3), p.275-280
Main Authors: 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
Format: Article
Language:English
Subjects:
Amino acids
Biological and medical sciences
Biotechnology
Cloning
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
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 Fingers - genetics
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Summary: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.
ISSN:1087-0156
1546-1696
DOI:10.1038/nbt796