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PMID: 9971771 Published · ppublish English Journal Article

The chromatin structure of the long control region of human papillomavirus type 16 represses viral oncoprotein expression.

Journal of virology ·Vol. 73 ·No. 3 ·1999-03-00 ·Pages 1918-30

Stünkel W, Bernard HU

Abstract

The long control region (LCR) of human papillomavirus type 16 (HPV-16) has a size of 850 bp (about 12% of the viral genome) and regulates transcription and replication of the viral DNA. The 5' segment of the LCR contains transcription termination signals and a nuclear matrix attachment region, the central segment contains an epithelial cell-specific enhancer, and the 3' segment contains the replication origin and the E6 promoter. Here we report observations on the chromatin organization of this part of the HPV-16 genome. Treatment of the nuclei of CaSki cells, a cell line with 500 intrachromosomal copies of HPV-16, with methidiumpropyl-EDTA-Fe(II) reveals nucleosomes in specific positions on the LCR and the E6 and E7 genes. One of these nucleosomes, which we termed Ne, overlaps with the center of the viral enhancer, while a second nucleosome, Np16, overlaps with the replication origin and the E6 promoter. The two nucleosomes become positioned on exactly the same segments after in vitro assembly of chromatin on the cloned HPV-16 LCR. Primer extension mapping of DNase I-cleaved chromatin revealed Np16 to be positioned centrally over E6 promoter elements, extending into the replication origin. Ne covers the center of the enhancer but leaves an AP-1 site, one of the strongest cis-responsive elements of the enhancer, unprotected. Np16, or a combination of Np16 and Ne, represses the activity of the E6 promoter during in vitro transcription of HPV-16 chromatin. Repression is relieved by addition of Sp1 and AP-1 transcription factors. Sp1 alters the structure of Np16 in vitro, while no changes can be observed during the binding of AP-1. HPV-18, which has a similar arrangement of cis-responsive elements despite its evolutionary divergence from HPV-16, shows specific assembly in vitro of a nucleosome, Np18, over the E1 binding site and E6 promoter elements but positioned about 90 bp 5' of the position of Np16 on the homologous HPV-16 sequences. The chromatin organization of the HPV-16 and HPV-18 genomes suggests important regulatory roles of nucleosomes during the viral life cycle.

MeSH Terms
Chromatin/physiology Genes, Regulator Nucleosomes/physiology Oncogene Proteins, Viral/genetics Papillomaviridae/genetics Papillomavirus E7 Proteins Promoter Regions, Genetic Repressor Proteins Sp1 Transcription Factor/physiology Transcription Factor AP-1/physiology Transcription, Genetic Virus Assembly Virus Replication
Chemicals
Chromatin E6 protein, Human papillomavirus type 16 Nucleosomes Oncogene Proteins, Viral Papillomavirus E7 Proteins Repressor Proteins Sp1 Transcription Factor Transcription Factor AP-1 oncogene protein E7, Human papillomavirus type 16
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Stünkel W
Institute of Molecular and Cell Biology, National University of Singapore, Republic of Singapore.
Bernard H U
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.73.3.1918-1930.1999
Published
1999-03-00
Pages
1918-30
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC104433
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.73.3.1918-1930.1999 PMC Full Text View journal details
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