skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

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}
}
  • The 5{prime} region of the gene encoding human X chromosome-linked phosphoglycerate kinase 1 (PGK1) is a promoter-containing CpG island known to be methylated at 119 of 121 CpG dinucleotides in a 450-base-pair region on the inactive human X chromosome in the hamster-human cell line X8-6T2. Here the authors report the use of polymerase chain reaction-aided genomic sequencing to determine the complete methylation pattern of this region in clones derived form X8-6T2 cells after treatment with the methylation inhibitor 5-azacytidine. They fine (i) a clone showing full expression of human phosphoglycerate kinase is fully unmethylated in this region; (ii) clones notmore » expressing human phosphoglycerate kinase remain methylated at {approximately}50% of CpG sites, with a pattern of interspersed methylated (M) and unmethylated (U) sites different for each clone; (iii) singles, defined as M-U-M or U-M-U, are common; and (iv) a few CpG sites are partially methylated. The data are interpreted according to a model of multiple, autonomous CpG sites, and estimates are made for two key parameters, maintenance efficiency and de novo methylation efficiency. They also consider how the active region is kept free of methylation and suggest that transcription inhibits methylation by decreasing E{sub m} so that methylation cannot be maintained. Thus, multiple CpG sites, independent with respect to a dynamic methylation system, can stabilize two alternative states of methylation and transcription.« less
  • Genomic imprinting and monoallelic gene expression appear to play a role in human genetic disease and tumorigenesis. The human H19 gene, at chromosome 11p15, has previously been shown to be monoallelically expressed. Since CpG methylation has been implicated in imprinting, the authors analyzed methylation of H19 DNA. In fetal and adult organs the transcriptionally silent H19 allele was extensively hypermethylated through the entire gene and its promoter, and, consistent with a functional role for DNA methylation, expression of an H19 promoter-reporter construct was inhibited by in vitro methylation. Gynogenetic ovarian teratomas were found to contain only hypomethylated H19 DNA, suggestingmore » that the expressed H19 allele might be maternal. This was confirmed by analysis of 11p15 polymorphisms in a patient with Wilms tumor. The tumor had lost the maternal 11p15, and H19 expression in the normal kidney was exclusively from this allele. Imprinting of human H19 appears to be susceptible to tissue-specific modulation in somatic development; in one individual, cerebellar cells were found to express only the otherwise silent allele. Implications of these findings for the role of DNA methylation in imprinting and for H19 as a candidate imprinted tumor-suppressor gene are discussed. 57 refs., 7 figs.« less
  • The human ZFX, human ZFY, and mouse Zfx genes have CpG islands near their 5` ends. These islands are typical in that they span about 1.5 kb, contain transcription initiation sites, and encompass some 5` untranslated exons and introns. However, comparative nucleotide sequencing of these humans and mouse islands provided evidence of evolutionary conservation to a degree unprecedented among mammalian 5` CpG islands. In one stretch of 165 nucleotides containing 19 CpGs, mouse Zfx and human ZFX are identical to each other and differ from human ZFY at only 9 nucleotides. In contrast, we found no evidence of homologous CpGmore » islands in the mouse Zfy genes, whose transcription is more circumscribed than that of a human ZFX, human ZFY, and mouse Zfx. Using the isoschizomers HpaII and MspI to examine a highly conserved segment of the ZFX CpG island, we detected methylation on inactive mouse X-chromosomes. These observations parallel the previous findings that mouse Zfx undergoes X inactivation while human ZFX escapes it. 62 refs., 7 figs., 1 tab.« less
  • The intracellular antioxidant enzyme, catalase, is encoded by a gene whose level of expression in different organisms, including humans, varies with tissue-type. The {open_quotes}TATA-less{close_quotes} 5{prime} upstream region of the catalase gene, in mice and humans, contains a CpG island. Such CG-rich regions are target sites for cytosine methylation and have been implicated in tissue-specific gene expression. However, the methylation status of individual CpG dinucleotides and their significance in gene expression has not been established. A 275 bp fragment within the 5{prime} region of Cas-1 was evaluated for CpG methylation. HpaII digestion of genomic DNA, followed by polymerase chain reaction amplificationmore » (HpaII-PCR), suggests that at least one of three CCGG is not methylated in nine different somatic tissues that express this enzyme at various levels. In contrast, all three CCGG sites are methylated in DNA from sperm and spleen. Further examination of the methylation specificity of individual CCGG sites was conducted using sodium bisulfite modification of genomic DNA followed by HPaII-PCR. Sodium bisulfite modifies non-methylated cytosines to uracils, changing a CG to a TG dinucleotide. This nucleotide substitution eliminates HpaII sites and allows the methylation status of each of the CCGG sites to be assessed. The ability to discern the number and combination of methylated sites within the 5{prime} region of a gene permits the determination of a possible correlation between differential methylation patterns and temporal/spatial gene regulation. Analysis of differential methylation, using the mouse catalase gene as a model, provides further insight into CpG methylation as one mechanism of mammalian gene regulation.« less