1
ToolGen Inc., 461-6
Jeonmin-Dong, Yusung-Gu, Daejeon,
305-390, South Korea.
2
School of Biological Sciences, Seoul National
University, Seoul, 151-742, South
Korea.
3
Department of Biochemistry and Institute of Basic
Medical Sciences and IFBB, Yonsei University, Wonju College of Medicine,
Wonju, 220-701, South Korea.
4
These authors contributed equally to this work.
Correspondence should be addressed to Jin-Soo Kim jsk@toolgen.com
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.
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