The recurrent issue about the members of the Ets family is their specificity for DNA binding. Even after close examination of the flanking sequences of a particular EBS, it is usually not possible to predict which Ets protein will bind to it. This is due to the fact, that (i) consensus-binding sequences are determined in vitro and correspond to high affinity-binding sites [13], which really seldom reflect physiological conditions, and (ii) Ets
MDV 3100 are known to often rely on binding partners to bind DNA [14], requiring longer DNA sequences for predicting DNA binding of Ets proteins in conjunction with potential partners. In this context, the present study shows another interesting aspect of Ets protein specificity. We previously suggested that EBS palindromes separated by 4 bp could serve as hot spots for recruitment of Ets-1 and Ets-2, proteins of the Ets family that are regulated by the same autoinhibition mechanism. Through these palindromes, Ets-1 and Ets-2 can bind to their target promoters without transcriptional-binding partners. Here, we extend this notion to promoters where an EBS is juxtaposed with a degenerate EBS, which is unable to bind Ets proteins. This is reminiscent of the Ets-1/Pax-5 interaction that enables Ets-1 to bind a degenerate EBS sequence in the immunoglobulin α-chain promoter [15]. Again, in the case of the EBS
palindrome separated by 4 bp, Ets-1 is able to play the role of its own partner.
