From enhancers to genome conformation: complex transcriptional control underlies expression of a single herpesviral gene.

ABSTRACT: Complex transcriptional control is a conserved feature of both eukaryotes and the viruses that infect them. Here, we illustrate this by combining high-density functional genomics, expression profiling, and viral-specific chromosome conformation capture to define with unprecedented detail the transcriptional regulation of a single gene, ORF68, from Kaposi's sarcoma-associated herpesvirus (KSHV). We first identified seven cis-regulatory regions by densely tiling the ~154 kb KSHV genome with CRISPRi. A parallel Cas9 nuclease screen indicated that three of these regions act as promoters of genes that regulate ORF68. RNA expression profiling demonstrated that three more of these regions act by either repressing or enhancing other distal viral genes involved in ORF68 transcriptional regulation.

SUBMITTER: Morgens DW 

PROVIDER: S-EPMC10350069 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature