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 hu man cytomegalovirus are known transcription factors, which regulate th e expression of viral and cellular genes. Transcriptional activation b y IE2 is dependent on the presence of a TATA motif in target promoters , and IE2 can interact directly with the TATA-binding protein (TBP) co mponent of TFIID. TBP is known to be the target for transcriptional re pression by the cellular Dr1 protein, and this factor has been shown t o repress expression from the hsp70 promoter in vivo. Since this promo ter 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 re pression 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 i s able to overcome this inhibition in vitro, suggesting a mechanism fo r the TATA dependency of IE2-mediated fr ans activation.