Resumen
Epigenetic reprogramming of the KSHV genome plays a central role in lytic replication of Kaposi?s sarcoma-associated herpesvirus (KSHV). Hypoxia, a common phenotype of cancer cells, exerts a negative effect on DNA replication. Interestingly, KSHV is known to bypass this repression and undergo lytic replication. Therefore, we investigated epigenetic reprogramming of the KSHV genome under hypoxic conditions. The KSHV genome was enriched with both transcriptional activator and repressor modifications of histones due to the upregulated expression of the modifying enzymes in KSHV-positive cells grown in hypoxia. KSHV-encoded antigens were responsible for this increase in modified histone proteins. The differential enrichment of KSHV-encoded LANA and RTA in hypoxia were suggestive of their role in transcriptional regulation. Furthermore, analysis investigating enrichment of DNA polymerase 1a on the KSHV genome in conjunction with single molecule analysis of replicated DNA identified specific regions of the KSHV genome that may be critical for DNA replication in hypoxia.