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Journal of Virology, February 2009, p. 1416-1421, Vol. 83, No. 3
0022-538X/09/$08.00+0 doi:10.1128/JVI.01276-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Gene Expression and Regulation Program, The Wistar Institute,1 Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennysylvania2
Received 19 June 2008/ Accepted 5 November 2008
It has been proposed that incorporation of the histone variant H3.3 within actively transcribed regions of a genome helps to facilitate transcription. In this report we use lytic infection by herpes simplex virus type 1 (HSV-1) as a model to examine the temporal profile of histone H3 incorporation and to determine whether the variant histone H3.3 has a direct effect on transcription. We find that canonical H3.1 and variant H3.3 exhibit distinct temporal associations with the genome in cell lines expressing equal amounts of epitope-tagged H3 variants. At the earliest times examined after infection, the HSV-1 genome is incorporated into chromatin that predominantly contains the variant H3.3, whereas incorporation of canonical H3.1 occurs later in infection and is dependent on replication of the HSV-1 genome. Further, inhibition of H3.3 association, via reduced expression of the H3.3 chaperone HIRA, significantly reduces the levels of HSV-1 mRNA. These findings show that incorporation of H3.3 facilitates transcription, and they provide new evidence for a regulatory role of chromatin composition during HSV-1 acute infection.
Published ahead of print on 12 November 2008.
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