The human cytomegalovirus 86-kilodalton major immediate-early protein interacts physically and functionally with histone acetyltransferase P/CAF

The major immediate-early proteins of human cytomegalovirus (HCMV) play a p ivotal role in controlling viral and cellular gene expression during produc tive infection. As well as negatively autoregulating its own promoter, the HCMV 86-kDa major immediate early protein (IE86) activates viral early gene expression and is known to be a promiscuous transcriptional regulator of c ellular genes. IEg6 appears to act as a multimodal transcription factor. It is able to bind directly to target promoters to activate transcription but is also able to bridge between upstream binding factors such as CREB/ATF a nd the basal transcription complex as well as interacting directly with gen eral transcription factors such as TATA-binding protein and TFIIB. We now s how that IE86 is also able to interact directly with histone acetyltransfer ases during infection. At Least one of these factors is the histone acetylt ransferase CBP-associated factor (P/CAF). Furthermore, we show that this in teraction results in synergistic transactivation by IE86 of IE86-responsive promoters. Recruitment of such chromatin-remodeling factors to target prom oters by IE86 may help explain the ability of this viral protein to act as a promiscuous transactivator of cellular genes.