The study of E1A-mediated trans-activation of adenovirus transcription has provided insight into mechanisms controlling transcription factor activity. Almost certainly, multiple cellular transcription factors contribute to the trans-activation process. At least two factors that appear to be essential for trans-activation, E2F and E4F, are regulated via changes in DNA binding activity, dependent on E1A action. The E2F factor is further regulated by a product of the early E4 gene. Two other factors, TFIIIC and a TATA specific factor, are clearly involved in E1A-dependent trans-activation, although the basis for their regulation is not yet clear. Thus, at least four cellular promoter specific transcription factors appear to be targets of the E1A pathway. Finally, indirect evidence suggests a mechanism of control whereby E1A might complex with a factor to contribute an acidic transcription activating domain.