Let your fingers do the walking

Transcription factors are often modular in nature, containing sequence-specific DNA binding domains and transactivation domains. In an Advanced Online Publication in Nature Biotechnology, Kwang-Hee Bae and colleagues at ToolGen Inc., South Korea, report the generation of "designer transcription factors" with specific binding activities (Nature Biotechnology, DOI:10.1038/nbt796, 18 February 2003).

A modified one-hybrid screen in yeast selected zinc fingers with specific DNA binding properties. The system was used to screen a library of over 2,000 factors that were derived from the Zif268 transcription factor and contained variant zinc finger sequences isolated from the human genome. Fifty six zinc fingers with distinct DNA-binding specificities were isolated. Bae et al. shuffled the selected zinc finger domains and tested them as transcription factors. They found that the "natural" human zinc finger domains function better than "artificial" engineered zinc fingers. The designer factors could also regulate expression of a chosen endogenous genomic locus.