HUMAN CYTOMEGALOVIRUS IE86 PROTEIN INTERACTS WITH PROMOTER-BOUND TATA-BINDING PROTEIN VIA A SPECIFIC REGION DISTINCT FROM THE AUTOREPRESSION DOMAIN

The major immediate-early gene of human cytomegalovirus encodes severa l isoforms of an immediate-early protein which has distinct transcript ional regulatory properties. The IE86 isoform autorepresses the major immediate-early promoter by directly binding the cis repression signal element located between the TATA box and the mRNA cap site. In additi on to this activity, IE86 stimulates other viral and cellular promoter s. One mechanism by which eukaryotic regulatory proteins are thought t o stimulate transcription is by contacting one or more general transcr iption factors. We show that the IE86 protein physically interacts wit h the DNA-binding subunit (TATA-binding protein) human transcription f actor IID via the TATA-binding protein-contacting domain in the N term inus of IE86. In a mobility shift assay, IE86 was also observed to sta bilize the binding of TATA-binding protein to promoter DNA. The domain s within IE86 responsible for mediating transactivation and repression functioned independently. These experiments thus demonstrate the eleg ant ability of human cytomegalovirus to join different protein domains to produce distinct multifunctional proteins.