Methods and compositions for interaction trap assays

A method for selecting a dimerizing polypeptide, comprising:

• providing a population of host cells wherein each host cell contains
• (a) a chimeric gene which encodes a fusion protein, including one or more zinc-finger DNA-binding domains, an activation domain that is heterologous to the DNA-binding domain, and a test polypeptide, wherein the chimeric gene is a member of a library comprising a plurality of randomly generated sequences test polypeptides;
• (b) a reporter gene operably linked to a transcriptional regulatory sequence which includes two or more binding sites (DBD recognition elements) for the DNA-binding domain of (a), wherein binding of a single copy of the fusion protein to the transcriptional regulatory sequence of the reporter gene does not result in a desired level of expression of the reporter gene;
• wherein dimerization of two copies of the fusion protein to each other and binding of the dimerized fusion protein to the transcriptional regulatory sequence of the reporter gene results in a desired level of expression of the reporter gene;
• and
• isolating host cells exhibiting a desired level of expression of the reporter gene thereby selecting a dimerizing polypeptide.