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Dynamic chromatin boundaries delineate a latency control region of Epstein-Barr virus.
J Virol. 2004 Nov; 78(22):12308-19.JV

Abstract

The oncogenic potential of latent Epstein-Barr virus (EBV) can be regulated by epigenetic factors controlling LMP1 and EBNA2 gene transcription. The EBV latency control region (LCR) constitutes approximately 12 kb of viral sequence spanning the divergent promoters of LMP1 and EBNA2 and encompasses the EBV latent replication origin OriP and RNA polymerase III-transcribed EBV-encoded RNA genes. We have used the chromatin immunoprecipitation assay to examine the chromatin architecture of the LCR in different types of EBV latency programs. We have found that histone H3 K4 methylation (H3mK4) was enriched throughout a large domain that extended from internal repeat 1 (IR1) to the terminal repeat in type III latency where EBNA2 and LMP1 genes are expressed. In type I latency where EBNA2 and LMP1 genes are transcriptionally silent, the H3mK4 domain contracts and does not enter the EBNA2 or LMP1 promoters. In contrast, histone H3 K9 methylation (H3mK9), associated with silent heterochromatin, was enriched in the EBNA2 and LMP1 upstream control regions in type I but not type III cells. MTA [5'-deoxy-5'(methylthio)adenosine], a pharmacological inhibitor of protein methylation, globally reduced histone H3mK4 and inhibited EBNA2 transcription in type III cells. 5'-Azacytidine, an inhibitor of DNA methylation that derepresses EBNA2 transcription in type I latency, caused H3mK4 expansion and a corresponding loss of H3mK9 at IR1. The chromatin boundary protein and transcription repressor CCCTC-binding factor was enriched at the EBNA2 transcription control region in type I but not type III cells. We also present evidence that OriP binding factors EBNA1 and ORC2 can interact with sequences outside of OriP including a region within IR1 that may influence EBNA2 transcription status. These results indicate that types I and III latency programs have distinct histone methylation patterns in the LCR and suggest that chromatin architecture coordinates gene expression of LMP1 and EBNA2.

Authors+Show Affiliations

The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15507618

Citation

Chau, Charles M., and Paul M. Lieberman. "Dynamic Chromatin Boundaries Delineate a Latency Control Region of Epstein-Barr Virus." Journal of Virology, vol. 78, no. 22, 2004, pp. 12308-19.
Chau CM, Lieberman PM. Dynamic chromatin boundaries delineate a latency control region of Epstein-Barr virus. J Virol. 2004;78(22):12308-19.
Chau, C. M., & Lieberman, P. M. (2004). Dynamic chromatin boundaries delineate a latency control region of Epstein-Barr virus. Journal of Virology, 78(22), 12308-19.
Chau CM, Lieberman PM. Dynamic Chromatin Boundaries Delineate a Latency Control Region of Epstein-Barr Virus. J Virol. 2004;78(22):12308-19. PubMed PMID: 15507618.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dynamic chromatin boundaries delineate a latency control region of Epstein-Barr virus. AU - Chau,Charles M, AU - Lieberman,Paul M, PY - 2004/10/28/pubmed PY - 2004/12/16/medline PY - 2004/10/28/entrez SP - 12308 EP - 19 JF - Journal of virology JO - J Virol VL - 78 IS - 22 N2 - The oncogenic potential of latent Epstein-Barr virus (EBV) can be regulated by epigenetic factors controlling LMP1 and EBNA2 gene transcription. The EBV latency control region (LCR) constitutes approximately 12 kb of viral sequence spanning the divergent promoters of LMP1 and EBNA2 and encompasses the EBV latent replication origin OriP and RNA polymerase III-transcribed EBV-encoded RNA genes. We have used the chromatin immunoprecipitation assay to examine the chromatin architecture of the LCR in different types of EBV latency programs. We have found that histone H3 K4 methylation (H3mK4) was enriched throughout a large domain that extended from internal repeat 1 (IR1) to the terminal repeat in type III latency where EBNA2 and LMP1 genes are expressed. In type I latency where EBNA2 and LMP1 genes are transcriptionally silent, the H3mK4 domain contracts and does not enter the EBNA2 or LMP1 promoters. In contrast, histone H3 K9 methylation (H3mK9), associated with silent heterochromatin, was enriched in the EBNA2 and LMP1 upstream control regions in type I but not type III cells. MTA [5'-deoxy-5'(methylthio)adenosine], a pharmacological inhibitor of protein methylation, globally reduced histone H3mK4 and inhibited EBNA2 transcription in type III cells. 5'-Azacytidine, an inhibitor of DNA methylation that derepresses EBNA2 transcription in type I latency, caused H3mK4 expansion and a corresponding loss of H3mK9 at IR1. The chromatin boundary protein and transcription repressor CCCTC-binding factor was enriched at the EBNA2 transcription control region in type I but not type III cells. We also present evidence that OriP binding factors EBNA1 and ORC2 can interact with sequences outside of OriP including a region within IR1 that may influence EBNA2 transcription status. These results indicate that types I and III latency programs have distinct histone methylation patterns in the LCR and suggest that chromatin architecture coordinates gene expression of LMP1 and EBNA2. SN - 0022-538X UR - https://www.unboundmedicine.com/medline/citation/15507618/Dynamic_chromatin_boundaries_delineate_a_latency_control_region_of_Epstein_Barr_virus_ L2 - http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=15507618 DB - PRIME DP - Unbound Medicine ER -