Snail1 (Snail) and Snail2 (Slug) are transcription factors that share a similar 
DNA binding structure of four and five C2H2 zinc finger motifs (ZF), 
respectively. Both factors bind specifically to a subset of E-box motifs 
(E2-box: CAGGTG/CACCTG) in target promoters like the E-cadherin promoter and are 
key mediators of epithelial-to-mesenchymal transition (EMT). However, there are 
differences in the biological actions, in binding affinities to E-cadherin 
promoter, and in the target genes of Snail1 and Snail2, although the molecular 
bases are presently unknown. In particular, the role of each Snail1 and Snail2 
ZF in the binding to E-boxes and in EMT induction has not been previously 
explored. We have approached this question by modeling Snail1 and Snail2 
protein-DNA interactions and through mutational and functional assays of 
different ZFs. Results show that Snail1 efficient repression and binding to 
human and mouse E-cadherin promoter as well as EMT-inducing ability require 
intact ZF1 and ZF2, while for Snail2, either ZF3 or ZF4 is essential for those 
functions. Furthermore, the differential distribution of E2-boxes in mouse and 
human E-cadherin promoters also contributes to the differential Snail factor 
activity. These data indicate a non-equivalent role of Snail1 and Snail2 ZFs in 
gene repression, contributing to the elucidation of the molecular differences 
between these important EMT regulators.