Function and Evolution of C2H2 Zinc Finger Arrays.

Krüppel-type or C2H2 zinc fingers represent a dominant DNA-binding motif in eukaryotic transcription factor (TF) proteins. In Krüppel-type (KZNF) TFs, KZNF motifs are arranged in arrays of three to as many as 40 tandem units, which cooperate to define the unique DNA recognition properties of the protein. Each finger contains four amino acids located at specific positions, which are brought into direct contact with adjacent nucleotides in the DNA sequence as the KZNF array winds around the major groove of the alpha helix. This arrangement creates an intimate and potentially predictable relationship between the amino acid sequence of KZNF arrays and the nucleotide sequence of target binding sites. The large number of possible combinations and arrangements of modular KZNF motifs, and the increasing lengths of KZNF arrays in vertebrate species, has created huge repertoires of functionally unique TF proteins. The properties of this versatile DNA-binding motif have been exploited independently many times over the course of evolution, through attachment to effector motifs that confer activating, repressing or other activities to the proteins. Once created, some of these novel inventions have expanded in specific evolutionary clades, creating large families of TFs that are lineage- or species-unique. This chapter reviews the properties and their remarkable evolutionary history of eukaryotic KZNF TF proteins, with special focus on large families that dominate the TF landscapes in different metazoan species.