Novel functions for the evolutionarily conserved Hexapeptide protein interaction motif in the control of Hox protein activity. Y. Graba ¹, S. Merabet ¹, Z. Kambris ², M. Cappovilla ², J. Pradel ¹. 1) LGPD/IBDM, CNRS, Campus Universitaire de Luminy, 13288 Marseille Cedex 09, France; 2) IBMC, CNRS 15, rue Ren Descartes 67084 Strasbourg Cedex,France.

   Hox proteins control diversified morphogenesis during development and evolution. They share the homeodomain and the hexapeptide, a motif known to raise Hox DNA-binding specificity in vitro. We report the first detailed analysis of the hexapeptide function in vivo. We found that the hexapeptide and linker region that connect the hexapeptide to the HD, act as intermediate regulatory modules, to sense cis-regulatory specificity and to select the repressive or activating potential of the Hox protein Abdominal-A. This is achieved by modulating the activity of repression and activation domains located N and C-terminal in the protein. Our in vivo data thus reveal novel functions, not anticipated from in vitro analyses, for the hexapeptide and linker region in Hox activity regulation.