Uneven distribution of methylation sites within the human papillomavirus la genome: possible relevance to viral gene expression.

A homogeneous preparation of human papillomavirus type 1a (HPV-1a) DNA resisted complete cleavage by the methylation-sensitive restriction endonuclease HhaI. Ten fragments additional to those predicted from the known HPV-1a DNA sequence were resolved by agarose gel electrophoresis of the HhaI-cleaved viral DNA. By determining the composite structures of the additional HhaI viral fragments, evidence was found for part-methylation of six of the thirteen HhaI sites. Two of the modified HhaI sites were localized to the 3'-end of the putative early gene region. The other four modified Hha-I sites were situated within the L1 open reading frame of the putative late gene region. Ten successive restriction endonuclease sites occurring close to and within an area of high CG density which surrounds the 5' end of the putative early gene region, were not modified detectably. The possible relevance of DNA methylation to the control of HPV-1a gene expression in epidermal cells is discussed.