Deep sequencing of large library selections allows computational discovery of diverse sets of zinc fingers that bind common targets.

ABSTRACT: The Cys2His2 zinc finger (ZF) is the most frequently found sequence-specific DNA-binding domain in eukaryotic proteins. The ZF's modular protein-DNA interface has also served as a platform for genome engineering applications. Despite decades of intense study, a predictive understanding of the DNA-binding specificities of either natural or engineered ZF domains remains elusive. To help fill this gap, we developed an integrated experimental-computational approach to enrich and recover distinct groups of ZFs that bind common targets. To showcase the power of our approach, we built several large ZF libraries and demonstrated their excellent diversity. As proof of principle, we used one of these ZF libraries to select and recover thousands of ZFs that bind several 3-nt targets of interest. We w

SUBMITTER: Persikov AV 

PROVIDER: S-EPMC3919609 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature