The human genome contains more than six ets-related genes )ETS1, ETS2, ERG, ERGB, ELK1, ELK2). In addition to having unique chromosomal locations, members of this ever-expanding gene family have unique patterns of expression. o understand the function(s) and mechanisms responsible for the functional differences between these genes, we intend to identify genes whose products are able to interact with ETS proteins. To achieve this goal, constructs containing defined segments of the open reading frames (ORF) from the human ETSI and ETS2 genes have been placed into prokaryotic vectors that allow for overexpression and rapid purification of the fusion protein produced by each construct. These vectors contain defined protein cleavage sites that allow for isolation of the unfused protein. These proteins will be labelled and utilized as probes to identify gene products (and the appropriate genes) with which they are able to interact. This methodology will be applied to other genes and will allow us to begin to dissect the role(s) of the ETS genes in the complex network of gene regulation and cellular signal transduc- tion.