CpG methylation suppresses transcriptional activity of human syncytin-1 in non-placental tissues.
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.
Matousková
Magda
M
Department of Cellular and Viral Genetics, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Flemingovo námìstí 2, 16637 Prague 6, Czech Republic.
Blazková
Jana
J
Pajer
Petr
P
Pavlícek
Adam
A
Hejnar
Jirí
J
D002460:Cell Line; D018899:CpG Islands / Q000502:physiology*; D019175:DNA Methylation; D015536:Down-Regulation / Q000235:genetics; D015686:Gene Products, env / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D010920:Placenta / Q000378:metabolism; D011257:Pregnancy Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D020079:Terminal Repeat Sequences; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics*; D014327:Trophoblasts / Q000378:metabolism
D015686:Gene Products, env; D011257:Pregnancy Proteins; D014157:Transcription Factors; C405335:syncytin