Motivation: Endogenous retrovirus (ERV) elements have been shown to contribute promoter sequences that can initiate transcription of adjacent human genes. However, the extent to which retroviral sequences initiate transcription within the human genome is currently unknown. We analyzed genome sequence and high-throughput expression data to systematically evaluate the presence of retroviral promoters in the human genome.
Results: We report the existence of 51,197 ERV-derived promoter sequences that initiate transcription within the human genome, including 1743 cases where transcription is initiated from ERV sequences that are located in gene proximal promoter or 5' untranslated regions (UTRs). A total of 114 of the ERV-derived transcription start sites can be demonstrated to drive transcription of 97 human genes, producing chimeric transcripts that are initiated within ERV long terminal repeat (LTR) sequences and read-through into known gene sequences. ERV promoters drive tissue-specific and lineage-specific patterns of gene expression and contribute to expression divergence between paralogs. These data illustrate the potential of retroviral sequences to regulate human transcription on a large scale consistent with a substantial effect of ERVs on the function and evolution of the human genome.