The Drosophila morphogenetic protein bicoid binds DNA cooperatively

The Drosophila morphogenetic protein Bicoid, encoded by the maternal gene bicoid, is required for the development of the anterior structures in the embryo. Bicoid, a transcriptional activator containing a homeodomain, is distributed in an anterior-to-posterior gradient in the embryo. In response to this gradient, the zygotic gene hunchback is expressed uniformly in the anterior half of the embryo in a nearly all-or-none manner. In this report we demonstrate that a recombinant Bicoid protein binds cooperatively to its sites within a hunchback enhancer element. A less than 4-fold increase in Bicoid concentration is sufficient to achieve an unbound/bound transition in DNA binding. Using various biochemical and genetic methods we further demonstrate that Bicoid molecules can interact with each other. Our results are consistent with previous studies performed in the embryo, and they suggest that one mechanism to achieve a sharp on/off switch of gene expression in response to a morphogenetic gradient is cooperative DNA binding facilitated by protein-protein interaction.