A deeper understanding of Hox specificity

A new level of understanding of Hox protein specificity in vivo is now described in this collaborative paper with Carlos Sánchez-Higueras and James C.-G. Hombria from the CSIC, Universidad Pablo de Olavide, Seville, Spain. In this paper, beautiful in vivo genetics is used to systematically vary Hox and Hox-cofactor binding sites in a cis-regulatory module from the ventral veinless (vvl) gene, which is normally under the control of multiple Hox proteins. By changing affinity and specificity of these binding sites, based entirely on our in vitro measurements, we have been able to generate enhancers with the predicted altered specificity in vivo. Surprisingly, this enhancer uses a combination of low affinity Hox-cofactor binding sites together with apparently monomeric binding sites to augment expression driven by a subset of Hox proteins.