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J Virol, April 1998, p. 2969-2974, Vol. 72, No. 4
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Specific Methylation Patterns in Two Control
Regions of Epstein-Barr Virus Latency: the LMP-1-Coding Upstream
Regulatory Region and an Origin of DNA Replication (oriP)
Kerstin I.
Falk,*
Laszlo
Szekely,
Anna
Aleman, and
Ingemar
Ernberg
Microbiology and Tumorbiology Center,
Karolinska Institute, S-171 77 Stockholm, Sweden
Received 22 October 1997/Accepted 5 January 1998
The Epstein-Barr virus (EBV) can establish at least four different
forms of latent infection. Previously, we have shown that the level of
methylation of the EBV genome varies, depending on the form of latency.
The methylation status of CpGs was analyzed by the bisulfite genomic
sequencing technique in four different cell types representing
different forms of latency. The dyad symmetry element of the origin of
replication (oriP) region and the latent membrane protein 1 (LMP-1)
regulatory sequence (LRS) were studied. The dyad symmetry element has
four binding sites for EBNA-1. In a cell with type I latency, a region
upstream of the dyad symmetry element was highly methylated, whereas
the dyad symmetry element was unmethylated in the EBNA-1-binding
region. The LRS was extensively methylated in the LMP-1-negative cell
line Rael, in contrast to a LMP-1-expressing nasopharyngeal carcinoma
tumor (NPC C15), which was almost completely unmethylated. The
methylation pattern of LRS in type I and type III Burkitt lymphoma
cells of similar parental origins confirmed that demethylation of some
regions takes place upon phenotypic drift.
*
Corresponding author. Mailing address: Microbiology and
Tumorbiology Center, Karolinska Institute, S-171 77 Stockholm, Sweden. Phone: 46-8-728-6286. Fax: 46-8-319470. E-mail:
Kerstin.Falk.{at}mtc.ki.se
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