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The Epstein-Barr virus episome maneuvers between nuclear chromatin compartments during reactivation
Stephanie A. Moquin,
Samantha G. Fernanadez,
Alison A. McBride,
Katherine S Pollard,
JJ L. Miranda
Posted 17 Aug 2017
bioRxiv DOI: 10.1101/177345 (published DOI: 10.1128/JVI.01413-17)
Posted 17 Aug 2017
The human genome is structurally organized in three-dimensional space to facilitate functional partitioning of transcription. We learned that the latent episome of the human Epstein-Barr virus (EBV) preferentially associates with gene-poor chromosomes and avoids gene-rich chromosomes. Kaposi's sarcoma-associated herpesvirus behaves similarly, but human papillomavirus does not. Contacts localize on the EBV side to OriP, the latent origin of replication. This genetic element, and the EBNA1 protein that binds there, are sufficient to reconstitute chromosome association preferences of the entire episome. Contacts localize on the human side to gene-poor regions of chromatin distant from transcription start sites. Upon reactivation from latency, however, the episome moves away from repressive heterochromatin and toward active euchromatin. Our work adds three-dimensional relocalization to the molecular events that occur during reactivation. Involvement of a myriad of interchromosomal associations also suggests a role for this type of long-range association in gene regulation.
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