Long-distance communication: Looping of human papillomavirus genomes regulates expression of viral oncogenes

Abstract

High-risk human papillomaviruses (HPVs) are a major cause of cancers. HPVs infect epithelial cells, and viral oncogenes disrupt several cellular processes, including cell division, differentiation, and apoptosis. Expression of these oncogenes is relatively low in undifferentiated epithelial cells but increases in differentiating cells by unknown mechanisms. In a new study, Parish and colleagues unveil how two cellular proteins, CCCTC-binding factor (CTCF) and Yin Yang 1 (YY1), mediate looping of the HPV18 genome, which regulates expression of viral oncogenes in both dividing and differentiating epithelial cells.

Fig 1. A graphical representation of the HPV18 genome.

The E6 and E7 oncogenes are shown in red. The other early genes are shown in green, and the late genes are shown in blue. The LCR, which contains multiple YY1-binding sites, is shown in yellow. The CTCF-binding site in the E2 ORF is also noted (in black). CTCF, CCCTC-binding factor; HPV, human papillomavirus; LCR, long control region; YY1, Yin Yang 1.