Yeast two-hybrid analysis. (a) The goal is to bring together the DNA-binding domain and the activation domain of the yeast Gal4 protein (Gal4p) through the interaction of two proteins, X and Y, to which one or other of the domains is fused. This interaction is accompanied by the expression of a reporter gene. (b) The two gene fusions are created in separate yeast strains, which are then mated. The mated mixture is plated on a medium on which the yeast cannot survive unless the reporter gene is expressed. Thus, all surviving colonies have interacting fusion proteins. Sequencing of the fusion proteins in the survivors reveals which proteins are interacting.