Human zinc fingers as building blocks in the construction of artificial transcription factors

Nat Biotechnol. 2003 Mar;21(3):275-80. doi: 10.1038/nbt796. Epub 2003 Feb 18.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / chemistry
  • DNA / genetics
  • DNA / metabolism
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • Gene Expression Regulation*
  • Genome, Human
  • Humans
  • Peptide Library*
  • Protein Engineering / methods
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Transcription Factors / biosynthesis*
  • Transcription Factors / chemistry
  • Transcription Factors / genetics*
  • Transcription, Genetic
  • Yeasts / genetics
  • Yeasts / metabolism
  • Zinc Fingers / genetics*


  • DNA-Binding Proteins
  • Peptide Library
  • Recombinant Proteins
  • Transcription Factors
  • DNA