ASSOCIATION OF THE HUMAN-PAPILLOMAVIRUS TYPE-11 E1 PROTEIN WITH HISTONE H1

The E1 and E2 proteins are the only virus-encoded factors I required f or human papillomavirus (HPV) DNA replication, The E1 protein is a DNA helicase responsible for initiation of DNA replication at the viral o rigin, Its recruitment to the origin is facilitated by binding to E2, for which specific recognition elements are located at the origin, The remaining replication functions for the virus, provided by the host c ell's replication machinery, may be mediated by further interactions w ith E1 and E2, Histone H1 was identified as an HPV type 11 (HPV-11) E1 -binding protein by far-Western blotting and by microsequence analyses of a 34-kDa protein purified by E1 affinity chromatography. E1 also b ound in vitro to H1 isolated under native conditions in association wi th intact nucleosomes. In addition, E1 and H1 were coimmunoprecipitate d by an E1 antiserum from a nuclear extract prepared from cells expres sing recombinant E1, Bound H1 was displaced fi om HPV-11 DNA bg the ad dition of E1, suggesting that F1 can promote replication initiation an d elongation by alteration of viral chromatin structure and disruption of nucleosomes at the replication fork, Furthermore, a region of the HPV-11 genome containing the origin of replication was identified whic h had weaker affinity for H1 than that of the remaining genome, This r esult suggests that the presence of a DNA structure at or near the HPV origin facilitates initiation of DNA replication by exclusion of H1, These results are similar to those of studies of simian virus 40 DNA r eplication, in which a large T antigen-H1 interaction and an Hi-resist ant region at the origin of DNA replication have also been demonstrate d.