Global epigenomic analysis of KSHV-infected primary effusion lymphoma identifies functional <i>MYC</i> superenhancers and enhancer RNAs
Angela Park, Soohwan Oh, Kyle L. Jung, Un Yung Choi, Hye-Ra Lee, Michael G. Rosenfeld, Jae U. Jung
Abstract
Significance Enhancers are crucial regulatory elements that dictate cellular processes by spatiotemporally controlling promoter activity. Recent studies have shown that active enhancers themselves generate noncoding enhancer RNAs (eRNAs) that play a critical role in fine tuning gene expression. Using genomic approaches, we demonstrate that oncogenic KSHV modulates host enhancer activity in PELs to control its lifecycle. During KSHV latency, expression levels of several key transcription factors and oncogenes are elevated by clusters of enhancers. Upon virus reactivation, global host enhancer activities are suppressed in order to facilitate viral replication. Our results indicate that better understanding and targeting host enhancer and eRNA functions may lead to novel therapeutics for PELs.