THE ABD-B-LIKE HOX HOMEODOMAIN PROTEINS CAN BE SUBDIVIDED BY THE ABILITY TO FORM COMPLEXES WITH PBX1A ON A NOVEL DNA TARGET

Previous studies showed that the Hox homeodomain proteins from paralog groups 1-8 display cooperative DNA binding with the non-Hox homeodoma in protein Pbx, mediated by a canonical YPWM. Although the Abd-B-like Hox proteins in paralogs 9-13 lack this sequence, Hoxb-9 and Hoxa-10 w ere reported to bind with Pbx1a to DNA. We show that these interaction s require a tryptophan 6 amino acids N-terminal to the homeodomain, Bi nding site selection for Hoxb-9 with Pbx1a yielded ATGATTTACGAC, conta ining a novel TTAC Hox-binding site adjacent to a Pbx site, In the pre sence of Pbx1a, Hoxb-9 and Hoxa-10 bound to targets containing either TTAC or TTAT. These data extend previous findings that interactions wi th Pbx define a Hox protein binding code for different DNA sequences a cross paralog groups 1 through 10. Members of the 11, 12, and 13 paral ogs do not cooperatively bind DNA with Pbx1a, despite the presence of tryptophan residues N-terminal to the homeodomain in Hoxd-12 and Hoxd- 13. Hoxa-11, Hoxd-12, or Hoxd-13, in the presence of Pbx1a, selected a TTAC Hox site but lacking a Pbx1a site, These data suggest that Abd-B -like Hox proteins bind to a novel TTAC site and can be divided by the ir cooperative binding to DNA with Pbx1a.