Krüppel-like Factors: Three Fingers in Many Pies

Kru ppel-like factors (KLFs) 1 are DNA-binding transcriptional regulators that play diverse roles during differentiation and development. They form a subset of the broad class of proteins containing Cys 2 /His 2 zinc fingers, a motif that is the second most abundant seen in the human genome and the most abundant in transcription factors, estimated to be present in just under 600 to over 700 proteins (1-3). The nomenclature is based on the homology of its founding member, EKLF (erythroid Kru ppel-like factor; KLF1), to the Drosophila Kru ppel protein (4). There are numerous finger proteins with such homology; however, the fact that KLF proteins contain additional conserved residues between each finger, that their fingers are three in number, and that these are found at the extreme carboxyl end serves to further define KLF proteins as a separate family (Fig. Phylogenetic analysis of the 15 human KLF members demonstrates that they form a clade distinct even from the closely related Sp1 and Krox zinc finger families. Structural considerations also place these members together, as three amino acids at specific locations ("XYZ" positions ( As a result, all members of the family bind very similar "GT-box" or "CACCC element" sites on DNA, although the configuration is such that the site tends to be C-rich on one strand and G-rich on the other.