Pathways to Specificity of ETS proteins

We have set as a long-term goal to understand how a family of highly related DNA binding factors is utilized in biological regulation using the ETS family as a model system. Do individual ETS proteins have unique roles or are there redundancies of function within the family? Specificity would require both a divergence of functionality of individual family members as well as pathways to direct different family members to different gene promoter targets. We have recently described that there is extensive co-expression of ETS family members in a diverse sampling of human cell types. Analysis of promoter targets in several of the cell types shows that, in some cases, there is specific matching between specific ETS proteins and specific targets. In other cases, there is co-occupancy by multiple ETS proteins at a specific promoter (Hollenhorst et al. 2004). We are currently investigating mechanisms of specificity at these different classes of promoters.