A puzzling property of the transcriptional activators encoded by several animal viruses is their ability to function promiscuously. The adenovirus E1a protein, for example, stimulates transcription of adenoviral genes as well as a wide variety of other viral and cellular genes. We show that E1a can interact with several classes of cellular DNA-binding domains and thereby be recruited to diverse promoters. Our results explain how a single protein can regulate transcription of multiple genes that lack a common promoter element.