Papillomavirus infection causes persistent epithelial lesions, known as papillomas. Papillomavirus infection is also associated with the development of cervical cancer. Our laboratory has established that papillomavirus genomes and the E2 transactivator protein interact with cellular mitotic chromosomes in dividing cells. This ensures that viral genomes are properly segregated to daughter cells and are retained within the nucleus.
Our aim i s to elucidate the mechanisms by which the E2 proteins control the viral life cycle. We have identified persistent and distinctive chromatin binding sites for the E2-Brd4 complex on human chromosomes. These novel sites persist in both interphase and mitotic cells. We propose that the viral DNA is tethered to these sites to maintain and partition the genomes. Understanding how the virus takes advantage of the inherent properties of the Brd4 protein is greatly increasing our understanding of epigenetic regulation and memory of the human genome. Comparative sequence and structural analysis of E2 proteins from different HPVs is providing insight into different mechanisms of persistent viral infection.
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