Deciphering the code for retroviral integration site selection

Upon cell invasion, retroviruses integrate the retroviral cDNA within the host chromosomal DNA. Integration occurs throughout the host cell genome but little is known about how integration sites are selected. The approach we propose is to identify markers predictive of retroviral integration. ChIPSeq datasets for more than 60 factors were compared with 14 retroviral integration data sets. By combining peaks from ChIPSeq datasets, a supermarker was identified that localized within 2 kB of 75% of gamma-proviruses and detected differences in integration preferences among different cell types. Thus we applied these findings to study viral sequences acquired by the human genome over the course of evolution. Indeed, HERV-H gamma-proviruses were found to be highly associated with one retroviral marker but only in embryonic and induced stem cells. We also discovered that HERV-H is also highly and specifically transcribed in this kind of cells, suggesting a role for these viral elements during embryonic development