BET proteins target murine leukemia virus integration to transcription start sites

Background The selection of chromosomal targets for retroviral integration varies markedly, tracking with the genus of the retrovirus, suggestive of specific targeting by cellular factors. Gamma-retroviral murine leukemia virus (MLV) DNA integration into the host genome is favored at transcription start sites, but the underlying mechanism for this preference is unknown. The molecular mechanisms of MLV integration are of particular significance due to the fact that MLV-based vectors are used for human gene-therapy. In clinical trials the use of MLV-based vectors to correct primary immunodeficiencies has been curative, but adverse events have occurred that are associated with the insertional activation of proto-oncogenes. Therefore the identification of cellular factors that control MLV integration may provide mechanistic clues to facilitate the development of safer gene-therapy vectors.