Activation of HIV-1 proviruses increases downstream chromatin accessibility
Raven Shah, Christian M. Gallardo, Yoonhee Jung, Ben Clock, Jesse R. Dixon, William M. McFadden, Kinjal Majumder, David J. Pintel, Victor G. Corces, Bruce E. Torbett, Philip R. Tedbury, Stefan G. Sarafianos
Abstract
It is unclear how the activation of HIV-1 transcription affects chromatin structure. We interrogated chromatin organization both genome-wide and nearby HIV-1 integration sites using Hi-C and ATAC-seq. In conjunction, we analyzed the transcription of the HIV-1 genome and neighboring genes. We found that long-range chromatin contacts did not differ significantly between uninfected cells and those harboring an integrated HIV-1 genome, whether the HIV-1 genome was actively transcribed or inactive. Instead, the activation of HIV-1 transcription changes chromatin accessibility immediately downstream of the provirus, demonstrating that HIV-1 can alter local cellular chromatin structure. Finally, we examined HIV-1 and neighboring host gene transcripts with long-read sequencing and found populations of chimeric RNAs both virus-to-host and host-to-virus. Thus, multiomics profiling revealed that the activation of HIV-1 transcription led to local changes in chromatin organization and altered the expression of neighboring host genes.