Presentation
In addition to the regulatory elements within the HIV-1 5’LTR promoter, viral transcription is also regulated by an intragenic cis-regulatory region (IRR) acting as an enhancer on the 5’LTR. Using Micro-Capture-C (MCC), we recently demonstrated the first evidence of a short-range IRR-5’LTR chromatin contact within the HIV-1 genome. In the project, using MCC, we will extend this finding both, in vitro using primary CD4+ T cells and macrophages models of HIV-1 infection, and ex vivo using HIV-1+ individuals-derived cells. Then, we will investigate the role of the structural factors YY1 and CTCF, in mediating this contact, using knockdown and site-directed mutagenesis approaches. Throughout this study, HIV-1 expression, chromatin accessibility and the IRR-5’LTR contact will be assessed by ChIP/RT-qPCR, ATAC-seq and MCC. Overall, this study will advance our understanding of HIV-1 gene regulation and may identify new drug targets for innovative therapeutic strategies against HIV-1 infection.
Promoters
- James Davies, MRC Weatherall Institute of Molecular Medicine, University of Oxford
- Carine Van Lint, Service of Molecular Virology, Department of Molecular Biology, ULB