Genome-Wide Binding Map of the HIV-1 Tat Protein to the Human Genome

The HIV-1 Trans-Activator of Transcription (Tat) protein binds to multiple host cellular factors and greatly enhances the level of transcription of the HIV genome While Tat's control of viral transcription is well-studied much less is known about the interaction of Tat with the human genome Here we report the genome-wide binding map of Tat to the human genome in Jurkat T cells using chromatin immunoprecipitation combined with next-generation sequencing Surprisingly we found that similar to 53% of the Tat target regions are within DNA repeat elements greater than half of which are Alu sequences The remaining target regions are located in introns and distal intergenic regions; only similar to 7% of Tat-bound regions are near transcription start sites (TSS) at gene promoters Interestingly Tat binds to promoters of genes that in Jurkat cells are bound by the ETS1 transcription factor the CBP histone acetyltransferase and/or are enriched for histone H3 lysine 4 tri-methylation (H3K4me3) and H3K27me3 Tat binding is associated with genes enriched with functions in T cell biology and immune response Our data reveal that Tat's interaction with the host genome is more extensive than previously thought with potentially important implications for the viral life cycle