Promoter specific regulation of Hox transregulatory properties by the Hexapeptide and linker region. S. Merabet , J. Pradel , Y. Graba. Campus Luminy, CNRS/LGPD, Marseille Provenc, France.

   While individual Hox proteins recognize similar target sequences, they attain specificity by interacting with additional cofactors of the Exd/Pbc family. This interaction is mediated by an evolutionary conserved hexapeptide motif. This motif, separated from the HD by a short "linker region", has been shown in vitro and in cell culture experiments to play a fundamental role in Hox target selectivity. Here we report on the functional contribution of the hexapeptide motif to AbdominalA (AbdA) Hox protein during Drosophila embryonic development. Surprisingly we found that, mutation of the hexapeptide motif apparently does not alter target gene selectivity. Instead, it is responsible to define, in a promoter specific manner, the activating or repressive action of AbdA. We found an additional conserved motif within the linker region that also specifies the transcriptional properties of AbdA. In summary, our data assign an in vivo unexpected function to the hexapeptide and "linker region" in the control of Hox regulatory activity rather than in target gene selectivity, and provide strong physiological evidence for the "Hox activity regulation" model.