DOI: 10.1128/jvi.78.22.12566-12575.2004. ORC, MCM, and Histone Hyperacetylation at the Kaposi's Sarcoma-Associated Herpesvirus Latent Replication Origin

ORC, MCM, and Histone Hyperacetylation at the Kaposi's Sarcoma-Associated Herpesvirus Latent Replication Origin

10.1128/jvi.78.22.12566-12575.2004

Crossref journal-article

American Society for Microbiology

Journal of Virology (235)

Abstract

ABSTRACT The viral genome of Kaposi's sarcoma-associated herpesvirus (KSHV) persists as an extrachromosomal plasmid in latently infected cells. The KSHV latency-associated nuclear antigen (LANA) stimulates plasmid maintenance and DNA replication by binding to an ∼150-bp region within the viral terminal repeats (TR). We have used chromatin immunoprecipitation assays to demonstrate that LANA binds specifically to the replication origin sequence within the KSHV TR in latently infected cells. The latent replication origin within the TR was also bound by LANA-associated proteins CBP, double-bromodomain-containing protein 2 (BRD2), and the origin recognition complex 2 protein (ORC2) and was enriched in hyperacetylated histones H3 and H4 relative to other regions of the latent genome. Cell cycle analysis indicated that the minichromosome maintenance complex protein, MCM3, bound TR in late-G 1 /S-arrested cells, which coincided with the loss of histone H3 K4 methylation. Micrococcal nuclease studies revealed that TRs are embedded in a highly ordered nucleosome array that becomes disorganized in late G 1 /S phase. ORC binding to TR was LANA dependent when reconstituted in transfected plasmids. DNA affinity purification confirmed that LANA, CBP, BRD2, and ORC2 bound TR specifically and identified the histone acetyltransferase HBO1 (histone acetyltransferase binding to ORC1) as a potential TR binding protein. Disruption of ORC2, MCM5, and HBO1 expression by small interfering RNA reduced LANA-dependent DNA replication of TR-containing plasmids. These findings are the first demonstration that cellular replication and origin licensing factors are required for KSHV latent cycle replication. These results also suggest that the KSHV latent origin of replication is a unique chromatin environment containing histone H3 hyperacetylation within heterochromatic tandem repeats.

Bibliography

Stedman, W., Deng, Z., Lu, F., & Lieberman, P. M. (2004). ORC, MCM, and Histone Hyperacetylation at the Kaposiâs Sarcoma-Associated Herpesvirus Latent Replication Origin. Journal of Virology, 78(22), 12566â12575.

Authors 4

William Stedman (first)
Zhong Deng (additional)
Fang Lu (additional)
Paul M. Lieberman (additional)

References 65 Referenced 155

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Dates

Type	When
Created	20 years, 10 months ago (Oct. 26, 2004, 5:49 p.m.)
Deposited	3 years, 5 months ago (March 5, 2022, 3:54 a.m.)
Indexed	14 minutes ago (Aug. 30, 2025, 9:31 p.m.)
Issued	20 years, 9 months ago (Nov. 15, 2004)
Published	20 years, 9 months ago (Nov. 15, 2004)
Published Print	20 years, 9 months ago (Nov. 15, 2004)

Funders 0

None

BibTeX

@article{Stedman_2004, title={ORC, MCM, and Histone Hyperacetylation at the Kaposi’s Sarcoma-Associated Herpesvirus Latent Replication Origin}, volume={78}, ISSN={1098-5514}, url={http://dx.doi.org/10.1128/jvi.78.22.12566-12575.2004}, DOI={10.1128/jvi.78.22.12566-12575.2004}, number={22}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Stedman, William and Deng, Zhong and Lu, Fang and Lieberman, Paul M.}, year={2004}, month=nov, pages={12566–12575} }

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