DNA-protein interaction is dominated by short anchoring elements

ABSTRACT To understand the regulation of gene expression, it is essential to elucidate the binding mechanism of DNA binding domain (DBD) of transcription factors (TFs), and predict the location of transcription factor binding sites (TFBSs). For an exhaustive search of TFBSs, we have investigated four typical TFs with diverse origins, such as WRKY, PU.1, GLUCOCORTICOID RECEPTOR (GR), and MYC2 by using a newly developed method, KaScape. During KaScape experiments, we identified short sequences (3-4 bases) or “anchoring element” (AE) for the four TFs that dominated the bound population of DNA-DBD binding. We further developed the AEEscape (AE Energy landscape) algorithm to detect and confirm the AE and derived its binding energy landscape for all possible sequences. Our analysis of the energy landscape revealed an energetic funnel around the TFBS, which is related to the AE density gradient in the region surrounding the TFBS. Our results provide novel insights into the mechanism of TF binding to TFBSs.