(13/n) Often, these alternative DNA-binding sets correspond to internal duplications, followed by divergence of the motifs recognized by these paralogous ZF arrays. We think these internal duplications play a major role in the evolution of novel functions for these TFs.

(12/n) When we applied RCADEEM to the GHT-SELEX data, we saw that not some, but in fact most of the TFs from the C2H2-ZF family use alternative sets of their ZF domains to bind to different DNA molecules.

(8/n) Surprisingly, for many TFs, we found a striking overlap between top GHT-SELEX and ChIP-seq peaks, suggesting these TFs intrinsically specify their binding sites independent of chromatin organization or other factors.

(6/n) Applying GHT-SELEX/MAGIX on 179 TFs, most of which were previously uncharacterized, we found that the majority do bind to the genome with high specificity, forming "peaks" that resemble those seen in vivo using ChIP-seq.

(5/n) But we can only know for sure by testing the binding of the TF to the genome directly, in the absence of other factors; i.e., in vitro. And that's what GHT-SELEX does. Together with a new statistical method we call MAGIX, GHT-SELEX identifies intrinsic binding sites of TFs on the genome.