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: Magda Matousková, Jana Blazková, Petr Pajer, Adam Pavlícek, Jirí Hejnar
• Journal: Experimental cell research (Exp Cell Res) Vol. 312 Issue 7 Pg. 1011-20 (Apr 15 2006) ISSN: 0014-4827 [Print] United States
• PMID: 16427621 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Gene Products, env
• Pregnancy Proteins
• Transcription Factors
• syncytin

Topics

• Cell Line
• CpG Islands (physiology)
• DNA Methylation
• Down-Regulation (genetics)
• Gene Products, env (antagonists & inhibitors, biosynthesis, genetics)
• HeLa Cells
• Humans
• Placenta (metabolism)
• Pregnancy Proteins (antagonists & inhibitors, biosynthesis, genetics)
• Promoter Regions, Genetic
• Terminal Repeat Sequences
• Transcription Factors (antagonists & inhibitors, biosynthesis, genetics)
• Trophoblasts (metabolism)