CpG methylation suppresses transcriptional activity of human syncytin-1 in non-placental tissues.
Exp Cell Res
; 312(7): 1011-20, 2006 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-16427621
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas da Gravidez
/
Fatores de Transcrição
/
Produtos do Gene env
/
Ilhas de CpG
/
Metilação de DNA
Limite:
Humans
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article