Δευτέρα 16 Δεκεμβρίου 2019

Chromatin maturation of the HIV provirus in primary resting CD4+ T cells

GSE121055 Chromatin maturation of the HIV provirus in primary resting CD4+ T cells: Contributors : Birgitta Lindqvist ; Sara S Akusjärvi ; Marios Dimitirou ; Anders Sönnerborg ; J P Svensson

Series Type : Genome binding/occupancy profiling by high throughput sequencing

Organism : Homo sapiens

Human immunodeficiency virus (HIV) infection is a chronic condition, where viral DNA integrates into the genome. The fate of the provirus determines the infection course. Latently infected cells form a persistent, heterogeneous reservoir. The reservoir that reinstates an active infection comprises cells with intact provirus that can be reactivated. We confirmed that latent cells from patients exhibited active transcription throughout the provirus. To find transcriptional determinants, we characterized the establishment and maintenance of latency during proviral chromatin maturation in primary CD4+ T-cells for four months after HIV infection. As heterochromatin (marked with H3K9me3 or H3K27me3) gradually stabilized, the provirus became less accessible and lost activation potential. In a subset of infected cells, active marks (i.e., H3K27ac) remained detectable, even after prolonged proviral silencing. After T-cell activation, the proviral activation occurred uniquely in cells with H3K27ac-marked proviruses. Our observations suggested that, after transient proviral activation, cells were actively returned to latency.

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