Epigenetic Control of Replication Origins

Efficient duplication of the eukaryotic genome requires the spatial and temporalcoordination of numerous replication origins on each chromosome. Epigenetic factors,like chromatin environment, can have profound effects on origin site selection, utilizationfrequency, and cell cycle firing time. Precisely how chromatin contributes to origin siteselection and timing is not completely understood. Recently, we reported on the cellcycle changes in chromatin structure at the plasmid replication origins of Epstein-BarrVirus (EBV) and Kaposi’s Sarcoma-Associated Herpesvirus (KSHV)1,2. These studiesand others suggest that cell cycle changes in histone modification and nucleosomeremodeling regulate pre-replication factor assembly and initiation of DNA replication atorigins. We discuss how these studies of viral origins may provide important insightsinto epigenetic control of cellular chromosome origins.