Showing papers by "Jin-Soo Kim published in 2003"
TL;DR: The 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: 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.
214 citations
TL;DR: The results show that randomized libraries of artificial transcription factors are useful tools for functional genomics and phenotypic engineering.
Abstract: We have developed a method in which randomized libraries of zinc finger-containing artificial transcription factors are used to induce phenotypic variations in yeast and mammalian cells. By linking multiple zinc-finger domains together, we constructed more than 100,000 zinc-finger proteins with diverse DNA-binding specificities and fused each of them to either a transcription activation or repression domain. The resulting transcriptional regulatory proteins were expressed individually in cells, and the transfected cells were screened for various phenotypic changes, such as drug resistance, thermotolerance or osmotolerance in yeast, and differentiation in mammalian cells. Genes associated with the selected phenotypes were also identified. Our results show that randomized libraries of artificial transcription factors are useful tools for functional genomics and phenotypic engineering.
158 citations
63 citations
TL;DR: Of 7458 genes in the microarray, it is found that genes involved in angiogenesis, defense against oxidative stress, and transcription regulation are severely impaired in senescent cell, which is consistent with the fact that aged cells have attenuated responses to various stimuli.
33 citations
TL;DR: Recent advances in the development of novel methods to design and construct artificial transcription factors to control gene expression at will are described and the applications in the areas of medicine and biotechnology are discussed.
Abstract: Expression of the genome is primarily regulated at the level of transcription by gene-specific transcription factors, which recognize specific DNA sequences to activate or inhibit transcription. The ability to control gene expression at will would provide scientists with a powerful tool for biotechnology and drug-discovery research. Over the last decade or so, researchers have made great strides in our understanding of the structures and mechanisms of action of naturally occurring transcription factors. Such research has revealed that members of the Cys2-His2 zinc finger family of transcription factors consist of functional modules that recognize a wide variety of DNA sequences. This review describes recent advances in the development of novel methods to design and construct artificial transcription factors to control gene expression at will. The applications of artificial transcription factors in the areas of medicine and biotechnology are discussed.
32 citations
TL;DR: The Pascal matrix and the Stirling matrices of the first kind and the second kind obtained from the Fibonacci matrix are studied, respectively and combinatorial identities from the matrix representation are obtained.
31 citations
TL;DR: The artificial transcription factor-based random genome perturbation method provides a novel functional genomic tool for annotation and classification of genes in the human genome and those of many other organisms.
Abstract: We have developed a novel, high-throughput approach to collecting randomly perturbed gene-expression profiles from the human genome.A human 293 cell library that stably expresses randomly chosen zinc-finger transcription factors was constructed, and the expression profile of each cell line was obtained using cDNA microarray technology.Gene expression profiles from a total of 132 cell lines were collected and analyzed by (1) a simple clustering method based on expression-profile similarity, and (2) the shortest-path analysis method. These analyses identified a number of gene groups, and further investigation revealed that the genes that were grouped together had close biological relationships. The artificial transcription factor-based random genome perturbation method thus provides a novel functional genomic tool for annotation and classification of genes in the human genome and those of many other organisms.
22 citations
TL;DR: In this paper, the linear algebra of the k-Fibonacci matrix and the symmetric k-fiboni matrix is discussed. But the authors do not discuss the properties of these matrices.
21 citations
Patent•
24 Sep 2003
TL;DR: The disclosure describes artificial chimeric transcription factors that include at least one zinc finger domain and that can regulate cellular differentiation, for example, a neuronal cell phenotype or an osteoblast phenotype as discussed by the authors.
Abstract: The disclosure describes artificial chimeric transcription factors that include at least one zinc finger domain and that can regulate cellular differentiation, for example, a neuronal cell phenotype or an osteoblast phenotype.
17 citations
Journal Article•
2 citations
Journal Article•