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Spatially clustered loci with multiple enhancers are frequent targets of HIV-1

ABSTRACT: 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 delineated with 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 activity 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE134382 | GEO | 2019/08/21

REPOSITORIES: GEO

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Project description:This SuperSeries is composed of the following subset Series: GSE10697: Self-Self Hybridisation were used to set confidence 99% intervals GSE10698: The effects of artificial tethering of chromosomes to the nuclear periphery using LacI/lap2b anchorage constructs 1 GSE10699: The effects of artificial tethering of chromosomes to the nuclear periphery using LacI/lap2b anchorage constructs 2 Background: The spatial organisation of the genome in the nucleus has a role in the regulation of gene expression. In mammals, chromosomal regions with low gene-density are located close to the nuclear periphery. Correlations have also been made between the transcriptional state of some genes and their location near the nuclear periphery. However, a crucial issue is whether this level of nuclear organisation directly affects gene function, rather than merely reflecting it. Methodology: To directly investigate whether proximity to the nuclear periphery can influence gene expression in mammalian cells. here we relocate specific human chromosomes to the nuclear periphery by tethering them to a protein of the inner nuclear membrane. Principal findings: We show that this can reversibly suppress the expression of some endogenous human genes located near the tethering sites, and even genes further away. However, the expression of many other genes is not detectably reduced and we show that location at the nuclear periphery is not incompatible with active transcription. The dampening of gene expression around the nuclear periphery is dependent on the activity of histone deacetylases. Significance: Our data show that the radial position within the nucleus can influence the expression of some, but not all, genes. This is compatible with the suggestion that re-localisation of genes to the peripheral zone of the nucleus could be used by metazoans to modulate the expression of selected genes during development and differentiation. Keywords: SuperSeries Refer to individual Series

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Spatially clustered loci with multiple enhancers are frequent targets of HIV-1

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