Cys2-His2 type zinc-finger proteins are the most common family of mammalian transcription factors. For transcriptional regulation, they recognize the target DNA sequences via three or more zinc-finger domains. Extensive contact with DNA via multiple zinc fingers allows highly specific DNA-binding, but can also slow the target search process. While both stability in target binding and rapidity in target search are important (particularly for inducible transcription factors), these two are mutually opposing issues (the speed-stability paradox). Using NMR and fluorescence methods, we have investigated how zinc-finger proteins scan DNA and locate their target sites. Our data for Egr-1 and Sp1 proteins suggest that domain motions play an important role in the DNA-scanning process, and that optimizing the domain dynamics of nonspecific DNA complexes can substantially improve the target search kinetics without diminishing specificity in binding. Application of the new knowledge to the zinc-finger technology will also be discussed.

DNA-scanning by zinc-finger proteins

246th National Meeting (2013)

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