ChIP seq of primary CD4+ T cells

HIV-1 recurrently targets active genes that are positioned in the outer shell of the nucleus and integrates in the proximity of the nuclear pore compartment. However, the genomic features of these genes and the relevance of their transcriptional activity for HIV-1 integration have so far remained unclear. Here we show that recurrently targeted genes are proximal to super-enhancer genomic elements and that they cluster in specific spatial compartments of the T cell nucleus. We further show that these gene clusters acquire their location at the nuclear periphery during the activation of T cells. The clustering of these genes along with their transcriptional status are the major determinants of HIV-1 integration in T cells. Our results show for the first time the relevance of the spatial compartmentalization of the genome for HIV-1 integration, thus further strengthening the role of nuclear architecture in viral infection. Overall design: Biological duplicates of H3K27Ac, repeated once as technical duplicates (2 samples sequenced 2 times), duplicates of H3K36me3 and H3K20me1. Triplicates of H3K4me3 and H3K9me2.