SEGMENTAL EXPRESSION OF HOXB-1 IS CONTROLLED BY A HIGHLY CONSERVED AUTOREGULATORY LOOP DEPENDENT UPON EXD PBX/

Comparison of Hoxb-1 regulatory regions from different vertebrates ide ntified three related sequence motifs critical for rhombomere 4 (r4) e xpression in the hindbrain. Functional analysis in transgenic mice and Drosophila embryos demonstrated that the conserved elements are invol ved in a positive autoregulatory loop dependent on labial (lab) family members. Binding of Hoxb-1 to these elements in vitro requires cofact ors, and the motifs closely resemble the consensus binding site for pb x1, a homolog of the Drosophila extradenticle (exd) homeodomain protei n. In vitro exd/pbx serves as a Hoxb-1 cofactor in cooperative binding and in Drosophila expression mediated by the r4 enhancer is dependent on both lab and exd. This provides in vivo and in vitro evidence that r4 expression involves direct autoregulation dependent on cooperative interactions of Hoxb-1 with exd/pbx proteins as cofactors.