Allele-specific long-distance regulation dictates IL-32 isoform switching and mediates susceptibility to HIV-1.

ABSTRACT: We integrated data obtained from HIV-1 genome-wide association studies with T cell-derived epigenome data and found that the noncoding intergenic variant rs4349147, which is statistically associated with HIV-1 acquisition, is located in a CD4⁺ T cell-specific deoxyribonuclease I hypersensitive region, suggesting regulatory potential for this variant. Deletion of the rs4349147 element in Jurkat cells strongly reduced expression of interleukin-32 (IL-32), approximately 10-kb upstream, and chromosome conformation capture assays identified a chromatin loop between rs4349147 and the IL-32 promoter validating its function as a long-distance enhancer. We generated single rs4349147-A or rs4349147-G allele clones and demonstrated that IL-32 enhancer activity and interaction with the IL-3

SUBMITTER: Palstra RJ 

PROVIDER: S-EPMC5833994 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature