Effect of integration of Human Papillomavirus on chromatin organisation in cervical cancer

Cervical cancer accounts to 90% of gynecological cancers worldwide. The major cause of the cancer is known to be Human papillomavirus (HPV). HPV is a DNA virus and has been known to integrate in the human genome causing gene alteration. Two major types of HPV known for its oncogenesis are HPV type 16 and 18. These viruses encode for two onco-proteins namely, E6 and E7 which are known to down-regulate the levels of p53 and pRB respectively and causes perturbed gene expression and uncontrolled cell division. Integration of such viral DNA can cause alteration in the overall conformation of the chromosome thereby leading to perturbed activity of gene expression by altering the TADs. It has been shown in previous studies that genes in particular TAD region will function either as enhancers, promoters or repressors. In order to identify the interaction of integrated viral E6 oncogene in human genome and also to study the function of TAD region containing viral oncogene, we used circular chromosome conformation capture (4C). We have identified the long range interaction of the E6 oncogene with various genes in the human genome. This study led to the conclusion that such integration has an altered effects on the overall expression of the onco-genes. Such interaction causes upregulation of certain proliferative and mitotic genes by interacting with it distantly thereby causing alteration in the TADs regions.