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Title: CpG methylation suppresses transcriptional activity of human syncytin-1 in non-placental tissues

Abstract

Syncytin-1 is a captive envelope glycoprotein encoded by one of human endogenous retroviruses W. It is expressed exclusively in the placental trophoblast where it participates in cell-to-cell fusion during differentiation of syncytiotrophobast. In other tissues, however, syncytin-1 expression must be kept in check because inadvertent cell fusion might be dangerous for tissue organization and integrity. We describe here an inverse correlation between CpG methylation of syncytin-1 5' long terminal repeat and its expression. Hypomethylation of the syncytin-1 5' long terminal repeat in the placenta and in the choriocarcinoma-derived cell line BeWo was detected. However, other analyzed primary cells and cell lines non-expressing syncytin-1 contain proviruses heavily methylated in this sequence. CpG methylation of syncytin-1 is resistant to the effect of the demethylating agent 5-azacytidine. The inhibitory role of CpG methylation is further confirmed by transient transfection of in-vitro-methylated syncytin-1 promoter-driven reporter construct. Altogether, we conclude that CpG methylation plays a principal role in the transcriptional suppression of syncytin-1 in non-placental tissues, and, in contrast, demethylation of the syncytin-1 promoter in trophoblast is a prerequisite for its expression and differentiation of multinucleated syncytiotrophoblast.

Authors:
 [1];  [1];  [2];  [1];  [3]
  1. Department of Cellular and Viral Genetics, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Flemingovo namisti 2, 16637 Prague 6 (Czech Republic)
  2. Department of Molecular Virology, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, 16637 Prague (Czech Republic)
  3. Department of Cellular and Viral Genetics, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Flemingovo namisti 2, 16637 Prague 6 (Czech Republic). E-mail: hejnar@img.cas.cz
Publication Date:
OSTI Identifier:
20775356
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 312; Journal Issue: 7; Other Information: DOI: 10.1016/j.yexcr.2005.12.010; PII: S0014-4827(05)00604-X; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; DNA; GLYCOPROTEINS; IN VITRO; INHIBITION; METHYLATION; PLACENTA; PROMOTERS

Citation Formats

Matouskova, Magda, Blazkova, Jana, Pajer, Petr, Pavlicek, Adam, and Hejnar, Jiri. CpG methylation suppresses transcriptional activity of human syncytin-1 in non-placental tissues. United States: N. p., 2006. Web. doi:10.1016/j.yexcr.2005.12.010.
Matouskova, Magda, Blazkova, Jana, Pajer, Petr, Pavlicek, Adam, & Hejnar, Jiri. CpG methylation suppresses transcriptional activity of human syncytin-1 in non-placental tissues. United States. doi:10.1016/j.yexcr.2005.12.010.
Matouskova, Magda, Blazkova, Jana, Pajer, Petr, Pavlicek, Adam, and Hejnar, Jiri. Sat . "CpG methylation suppresses transcriptional activity of human syncytin-1 in non-placental tissues". United States. doi:10.1016/j.yexcr.2005.12.010.
@article{osti_20775356,
title = {CpG methylation suppresses transcriptional activity of human syncytin-1 in non-placental tissues},
author = {Matouskova, Magda and Blazkova, Jana and Pajer, Petr and Pavlicek, Adam and Hejnar, Jiri},
abstractNote = {Syncytin-1 is a captive envelope glycoprotein encoded by one of human endogenous retroviruses W. It is expressed exclusively in the placental trophoblast where it participates in cell-to-cell fusion during differentiation of syncytiotrophobast. In other tissues, however, syncytin-1 expression must be kept in check because inadvertent cell fusion might be dangerous for tissue organization and integrity. We describe here an inverse correlation between CpG methylation of syncytin-1 5' long terminal repeat and its expression. Hypomethylation of the syncytin-1 5' long terminal repeat in the placenta and in the choriocarcinoma-derived cell line BeWo was detected. However, other analyzed primary cells and cell lines non-expressing syncytin-1 contain proviruses heavily methylated in this sequence. CpG methylation of syncytin-1 is resistant to the effect of the demethylating agent 5-azacytidine. The inhibitory role of CpG methylation is further confirmed by transient transfection of in-vitro-methylated syncytin-1 promoter-driven reporter construct. Altogether, we conclude that CpG methylation plays a principal role in the transcriptional suppression of syncytin-1 in non-placental tissues, and, in contrast, demethylation of the syncytin-1 promoter in trophoblast is a prerequisite for its expression and differentiation of multinucleated syncytiotrophoblast.},
doi = {10.1016/j.yexcr.2005.12.010},
journal = {Experimental Cell Research},
number = 7,
volume = 312,
place = {United States},
year = {Sat Apr 15 00:00:00 EDT 2006},
month = {Sat Apr 15 00:00:00 EDT 2006}
}