The Drosophila morphogenetic protein Bicoid, encoded by the maternal g
ene bicoid, is required for the development of the anterior structures
in the embryo. Bicoid, a transcriptional activator containing a homeo
domain, is distributed in an anterior-to-posterior gradient in the emb
ryo, In response to this gradient, the zygotic gene hunchback is expre
ssed uniformly in the anterior half of the embryo in a nearly all-or-n
one manner, In this report we demonstrate that a recombinant Bicoid pr
otein binds cooperatively to its sites within a hunchback enhancer ele
ment, A less than 4-fold increase in Bicoid concentration is sufficien
t to achieve an unbound/bound transition in DNA binding, Using various
biochemical and genetic methods we further demonstrate that Bicoid mo
lecules can interact with each other. Our results are consistent with
previous studies performed in the embryo, and they suggest that one me
chanism to achieve a sharp on/off switch of gene expression in respons
e to a morphogenetic gradient is cooperative DNA binding facilitated b
y protein-protein interaction.