Overexpression of C/EBPβ represses human papillomavirus type 18 upstream regulatory region activity in HeLa cells by interfering with the binding of TATA-binding protein

The human papillomavirus type 18 (HPV-18) upstream regulatory region (URR) controls cell type-specific expression of viral oncoproteins E6 and E7. The HPV-18 URR is highly active in HeLa cells, but its activity is virtually undetectable in HepG2 cells. Previous work has shown that YY1 plays an important role in activation of the HPV-18 URR in HeLa cells, and this activating activity is dependent on its physical interaction with C/EBP beta, which binds to the switch region adjacent to the YY1 site in the URR . Overexpression of C/EBP beta in HepG2 cells restores C/EBP beta-YY1 interaction, resulting in strong activation of the HPV-18 URR activity. In this report, we show that, in contrast to the effect in HepG2 cells, overexpression of C/EBP beta represses the HPV-18 URR in HeLa cells. This C/EBP beta-induced repression of the HPV-18 URR in HeLa cells is binding site independent, It is also promoter specific, since it activates the albumin promoter under conditions in which it represses the URR in the same cells. Biochemical analysis shows that overexpression of C/EBP beta in HeLa cells specifically interferes with binding of TATA-binding protein to the TATA box of the HPV-18 URR, but its overexpression in HepG2 cells leads to activation of the HPV-18 URR. These results suggest that a molecular mechanism underlies the ability of C/EBP beta to regulate transcription in a tell type-specific manner and indicate the potential of using C/EBP beta to manipulate the activity of the HPV-18 URR in cervical carcinoma cells.