E2 and the co-activator p300 can cooperate in activation of the human papillomavirus type 16 early promoter.

In addition to cellular transcription factors, the E2 protein encoded by human papillomaviruses (HPV) modulates the viral gene expression to support the life cycle of HPV, which depends on the differentiation of the infected keratinocytes. The role of E2 as activator of viral transcription still remains unsolved. We show here that low amounts of E2 encoded by HPV16 efficiently activated the early promoter P(97) of HPV16. In addition to the long control region, this activation required high amounts of the cellular co-activator p300 and a novel binding site for CCAAT enhancer-binding protein alpha (C/EBPalpha) located downstream of the P(97) at position 480. The expression of C/EBPalpha was shown previously to increase during keratinocyte differentiation. By immunohistochemistry we demonstrate that the expression of p300 is induced in suprabasal epithelial cells of HPV16 positive and negative squamous epithelium. Our data suggest that high levels of p300 and C/EBPalpha in suprabasal layers of HPV16 positive cervical lesions allow the viral E2 protein to activate HPV16 early gene expression.