Xl. Li et al., A sequence motif distinct from Hox binding sites controls the specificity of a Hox response element, DEVELOPMENT, 126(24), 1999, pp. 5581-5589
Hox transcription factors, in combination with cofactors such as PBC protei
ns, provide diverse developmental fates to cells on the anteroposterior bod
y axis of animal embryos. However, the mechanisms by which the different Ho
x proteins and their cofactors generate those diverse fates remain unclear.
Recent findings have provided support for a model where the DNA binding si
tes that directly interact with Hos-PBC heterodimers determine which member
of the Hox protein family occupies and thereby regulates a given target el
ement. In the experiments reported here, we test the function of chimeric H
ox response elements and, surprisingly, find evidence that runs counter to
this view. A 21 bp cofactor binding sequence from an embryonic Deformed Hox
response element, containing no Hox or Hox-PBC binding sites, was combined
with single or multimeric sites that bind heterodimers of Labial-type Hox
and PBC proteins. Normally multimerized Labial-PBC binding sites are suffic
ient to trigger a Labial-specific activation response in either Duosophila
or mouse embryos. Here we find that the 21 bp sequence element plays an imp
ortant role in Deformed specificity, as it is capable of switching a Labial
-PBC binding site/response element to a Deformed response element. Thus, co
factor binding sites that are separate and distinct from homeodomain bindin
g sites can dictate the regulatory specificity of a Hox response element.