The ETS family of transcription factors was found to be essential for many cellular functions and was involved in the development of diseases such as cancers. All the members of the ETS family recognize conserved DNA sequences with a helix-turn-helix motif at 5’-GGAA-3’ in the major groove and contact the flanking DNA sequences in the minor groove via phosphate backbone. Despite the exponential increase in knowledge on the molecular biology of this family, there is limited information on the mechanism how these structural conserved transcription factors find theirs target DNA site.<br/>Transcription factors and other DNA binding proteins can efficiently search for their target DNA via facilitated diffusion such as sliding, hopping, and intersegmental transfer. The mechanisms of sliding and hopping have been scrutinized with different proteins over the years and are well understood at the molecular level. Knowledge of the intersegmental transfer of proteins with a single DNA binding domain remains unveiled. We have developed a method using surface plasmon resonance (SPR) to examine the binding mechanism of ETS proteins to its DNA target site. In the previous study on ETV6, a member of ETS, we have shown that by changing salt concentration, we can directly observe the change in the mechanism that a protein initiates to find its target DNA. The results showed that target search by ETV6, which cannot contact the source and targeted DNA site spontaneously, still in fact governed by intersegmental transfer in a heterogeneous site environment. We have expanded the observation on four different ETS proteins that are evenly spaced on the evolutional phylogenetic tree. The structures and interactions of many of the ETS transcription factors with their cognate DNA sequences are now understood in detail.<br/><br/>

Electrostatic control of binding interactions between ETS transcription factors proteins and theirs cognate DNA

255th National Meeting (2018)

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