GSE137533 Global epigenomic analysis of primary effusion lymphoma identifies MYC super-enhancers and enhancer RNAs associated with KSHV infection

This study showed that a number of critical host genes for KSHV latency, including MYC proto-oncogene, were under the control of super-enhancers and eRNAs that were globally r epressed upon viral reactivation. A combination of circular chromosome conformation capture combined with sequencing (4C-seq), GRO-seq and ChIP-seq indicated that the eRNA-expressing super-enhance regions were located at downstream of the MYC gene in KSHV-infected PELs. Treatment of an epigenetic dr ug to block enhancer function or shRNA-mediated depletion of the eRNA expression significantly reduced MYC mRNA expression in KSHV-infected PELs. Finally, while cellular IRF4 acted upon the eRNAs and super-enhancers for MYC expression during latency, the KSHV viral IRF4 repressed cellular IRF4 expre ssion upon reactivation, decreasing MYC expression and thereby, facilitating lytic replication. Taken together, these data suggest that KSHV acts as an epigenetic driver that modifies host epigenomic status by effectively regulating enhancer function upon reactivation.

Source: GEO: Gene Expression Omnibus - September 17, 2019 Category: Genetics & Stem Cells Tags: Other Genome binding/occupancy profiling by high throughput sequencing Homo sapiens Source Type: research