Human cytomegalovirus immediate-early 2 (IE2) protein can transactivate the human hsp70 promoter by alleviation of Dr1-mediated repression

The immediate-early 1 and 2 (IE1 and IE2, respectively) proteins of human cytomegalovirus are known transcription factors, which regulate the expression of viral and cellular genes. Transcriptional activation by IE2 is dependent on the presence of a TATA motif in target promoters, and IE2 can interact directly with the TATA-binding protein (TBP) component of TFIID. TBP is known to be the target for transcriptional repression by the cellular Dr1 protein, and this factor has been shown to repress expression from the hsp70 promoter in vivo. Since this promoter is up-regulated by IE2, we asked whether the effects of Dr1 can be overcome by IE2. We report here that IE2 can overcome Dr1-mediated repression of the hsp70 promoter in vivo and that IE2 can interact with Dr1 in vivo and in vitro. We also demonstrate a previously unreported activity of Dr1, inhibition of DNA binding by TBP, and show that IE2 is able to overcome this inhibition in vitro, suggesting a mechanism for the TATA dependency of IE2-mediated fr ans activation.