ZF modules designed to target GNN, ANN, CNN and TNN sequences are randomized to create polydactyl ZF proteins (depicted is a six-ZF library). Each grey motif represents a module that can target any given triplet. More modules exist for targeting triplets beginning with purines than those beginning with pyrimidines. An ED, such as an AD (activation domain), is used to regulate genes. The library is tested in cells (depicted as fibroblasts or pluripotent cells) by transduction, and hits are selected by screening for a desired phenotype or activation of a lineage-specific gene. ATFs are recovered by sequencing integrated transgenes. Positive ATFs can then be validated for their cell fate-defining effects.