Binding properties of the human homeodomain protein OTX2 to a DNA target sequence

OTX2, a homeodomain protein essential in mouse far the development of struc tures anterior to rhombomere 3, binds with high affinity to a DNA clement ( caned OTS) present in the human tenascin-C promoter, Were we investigate th e binding properties of the full length recombinant human OTX2 and of sever al deletion mutants to the OTS element. We demonstrate that, upon binding o f the protein to its DNA target site, a second molecule of OTX2 is recruite d to the complex and that a nearby second binding site is not necessary for this interaction, OTX2 sequences located within a region carboxyl-terminal to the homeodomain are necessary in addition to the homeodomain for bindin g to DNA, Furthermore, OTX2 dimerization requires the same protein domains necessary for DNA binding. (C) 1999 Federation of European Biochemical Soci eties.