Our goal is to study the regulation of gene expression of DNA tumor virus genomes at the molecular level and to use this knowledge to understand the mechanisms of eukaryotic gene expression and virus-host cell interactions. The objectives are to study the transcriptional regulation of adenovirus type 5 early transcriptional region (EII) and to attempt to isolate and characterize the host genes activated by the viral pre-early EIA gene. Transcriptional control elements of the EIIA-late promoter will be identified at the virus level using the linker scanning mutagenesis approach. Functional relationship of the transcriptional control elements of the two DIIA (early and late) promoters and the genetic basis of their differential regulation in viral lytic cycle will be studied using novel mutant viruses. Biochemical approaches such as gel assays for DNA-protein complexes and in vivo assays involving exonuclease III will be employed to identify transcription factors which may interact wih the transcriptional control elements of the two EIIA promoters. Utilizing molecular hybridization and gene cloning techniques, attempts will be made to identify and isolate the host genes activated by the viral pre-early EIA gene.